November 2015

ISSN : 2200-9876

The official publication of the Australian and New Zealand Society of Nuclear Medicine

November 2015, Issue 16

Contents

www.anzsnm.org.au

Welcome

3

President’s Report

7

Branch News

ACT

8

New South Wales

8

New Zealand

8

Queensland

9

South Australia

9

Victoria/Tasmania 10

Western Australia

10

Technical Standards

12

SIG

CPD

13

Internal Dosimetry Assessment in Nuclear Medicine 14 Diary Dates

17

ANZSNM Annual General Meeting Minutes 18 Financials 20 Word Search 22 SIR-Spheres (90Y-microspheres) treatment featured at ASCO meeting 26 NET Update: Nuclear Medicine & Neuroendocrine Tumours 28 Case Studies

Assessment of Mucosa-associated Lymphoid Tissue (MALT) lymphoma using

[18F]-FDG PET/CT 32

The value of delayed 18F-FDG PET/CT imaging in metastatic colorectal carcinomar 34

Peer Reviewed

Lutetium-177 DOTATATE Production with an Automated Radio-pharmaceutical Synthesis System

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Deadlines The deadlines for each issue of Gamma Gazette for this year are set out below. These deadlines must be strictly adhered to in order to get the journal out on time. Do not leave the submission of copy until the last minute. For advice on how to submit material please go to the website www.anzsnm.org.au March – February 1

2

July – June 1

November – October 1

Welcome WELCOME to the November edition of the Gamma Gazette prepared and edited by the NSW Branch of the ANZSNM. The NSW Branch has undergone several changes in the last few months, most notably the resignation of our previous branch chair Ms Tracey Trevaskis. Tracey has been a long standing member of the NSW Branch of the ANZSNM and was the NSW representative on the Federal Council for several years. She worked tirelessly for the branch and its members and will be missed as a member of the committee.

Preparation for the ANZSNM ASM to be held in Rotorua New Zealand 22-25 April 2016 is progressing as planned with abstract submission and earlybird registration in October 2015. The ANZSNM have been engaging members to improve the functionality of the website and investigate new methods of providing CPD activities, as successfully done by the NSW Branch recently with the presentation given as a ‘green lecture’ by the international speaker live from Germany. It is hoped that this technology can be made available to other branches in the new year.

This issue includes several case studies, review articles on international relations, current research / collaborations, an update from ANSTO on Lu177 and the Moly facility and a scientific paper reprinted courtesy of the AOJNMB. We acknowledge contributions from the members and the NSW branch committee for preparing and reviewing the content.

Elizabeth Bailey NSW Branch Chairperson

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Journal Staff

Editorial copy & Advertising copy

Andrew St John General Manager ANZSNM Secretariat PO Box 6178, Vermont South, VIC 3133 Tel: 1300 330 402 Fax: (03) 8677 2970 Email: secretariat@anzsnm.org.au

The Australian and New Zealand Society of Nuclear Medicine Limited

Design & Production

Rachel Bullard Deep Blue Design Studio Email: deepbluedesign1@me.com

Aims and Objectives

The objectives of the Society are as follows: 1. Promote a) the advancement of clinical practice of nuclear

medicine in Australia and New Zealand;

b) research in nuclear medicine;

c) public education regarding the principles and

applications of nuclear medicine techniques in

medicine and biology at national and regional levels;

d) co-operation between organisations and individuals

interested in nuclear medicine; and

e) the training of persons in all facets of nuclear medicine.

This issue compiled by the New South Wales branch.

Submissions Scientific submissions on all aspects of nuclear medicine are encouraged and should be forwarded to the Secretariat (see instructions for authors published on line at www.anzsnm.org. au). Letters to the Editor or points of view for discussion are also welcome.

If original or public domain articles are found and considered to be of general interest to the membership, then they should be recommended to the Editor who may seek permission to reprint.The view expressed in any signed article in the journal do not necessarily represent those of the Society. The individual rights of all authors are acknowledged.

2. Provide opportunities for collective discussion on all or any aspect of nuclear medicine through standing committees and special interest groups: a) The Technical Standards Committee sets minimum

standards and develops quality control procedures

for nuclear medicine instrumentation in Australia

and New Zealand.

The ANZSNM Gamma Gazette is published three times a year: March, July and November.

Deadlines for each issue of the journal are the first of each month prior to publishing. Š 2015 The Australian and New Zealand Society of Nuclear Medicine Inc. Copyright is transferred to the Australian and New Zealand Society of Nuclear Medicine once an article/paper has been published in the ANZSNM Gamma Gazette (except where it is reprinted from another publication).

ANZSNM website address: www.anzsnm.org.au

4 Gamma Gazette November 2015

b) The Technologists Special Interest Group. With the introduction of National Registration for Nuclear Medicine Technologists / Scientists as of 1st July 2012, the future role of the Accreditation Board was reviewed and federal council made a decision to disband the current Accreditation Board and reallocate ongoing responsibilities to the ANZSNM – Technology Special Interest Group (TSIG). The PDY and mentor program, CPD program, department accreditation and the overseas qualification exam are now managed by sub-committees of the TSIG. 2) The Radiopharmaceutical Science SIG and a Physics SIG that maintain standards of practice for their particular speciality and provide a forum for development in Australia and New Zealand.

Office Bearers Any changes or additions to the details listed should be forwarded in writing to the Secretariat as soon as possible.

President Vice President Past President Treasurer Committee

Prof Vijay Kumar (IRC), email: vijay.kumar@health.nsw.gov.au Prof Dale Bailey (NSW), email: dale.bailey@sydney.edu.au Dr Elizabeth Bailey (TSIG), email: Elizabeth.Bailey2@health.nsw.gov.au Mr Dominic Mensforth (SA), email: dominic.mensforth@i-med.com.au A/Prof Roslyn Francis (WA), email: roslyn.francis@uwa.edu.au Dr Doug Smyth (Radiopharmaceutical Science Rep), email: Douglas.Smyth@health.sa.gov.au Dr Susan O’Malley (NZ), email: sue@omalley.co.nz Dr Sam Berlangieri (Physicians Rep), email: berlangieri@mac.com Ms Sharon Mosley (ACT), email: Sharon.Mosley@act.gov.au Mr David Thomas (VIC/TAS), email: David.Thomas@austin.org.au Dr Daniel Badger (SA), daniel.badger@health.sa.gov.au Ms Clare Radley (NZ), hairyfairy56_NZ@yahoo.co.nz

General Manager & Secretariat

Dr Andrew St John and Drajon Management Pty Ltd

All correspondence ANZSNM Secretariat

PO Box 6178, Vermont South VIC 3133 Tel: 1300 330 402 Fax: (03) 8677 2970 Email: secretariat@anzsnm.org.au Branch Secretaries Australian Capital Territory New South Wales Queensland South Australia Victoria/Tasmania Western Australia New Zealand

Ms Maree Wright, email: Maree.Wright@act.gov.au Dr Liz Bailey, email: Elizabeth.Bailey2@health.nsw.gov.au Mr James Turner and Mr Louis Gray, email: qldbranchsecretaryanzsnm@gmail.com Ms Kimberley Nguyen, email: kimberly.nguyen@bensonradiology.com.au Ms Jessica Welch, email: jessica.welch@austin.org.au Ms Georgina Santich, email: wabranchsecretary@hotmail.com Ms Pru Burns, email: pru.burns@prg.co.nz

Special Interest Groups Technologists Radiopharmaceutical/Science Physics/Computer Science Technical Standards Committee Scientific Advisory Panel International Relations Committee Nurse Member Liaison

Dr Elizabeth Bailey, email: Elizabeth.Bailey2@health.nsw.gov.au Dr Doug Smyth, email: Douglas.Smyth@health.sa.gov.au Dr Daniel Badger (SA), daniel.badger@health.sa.gov.au Chairperson: Dr Darin O’Keeffe, email: darin.okeeffe@cdhb.govt.nz Chairperson: Prof Dale Bailey, email: dale.bailey@sydney.edu.au Chairperson: Professor Andrew Scott, email: Andrew.Scott@ludwig.edu.au Mr Erwin Lupango, email: Erwin.lupango@sessiahs.health.nsw.gov.au

Reporting of Abnormal Behaviour of Radiopharmaceuticals The Society maintains a register of reports of abnormal behaviour of radiopharmaceuticals.

Abnormal behaviour can be reported either by telephone fax or e-mail, or in writing to: Dr John Baldas, ARPANSA Mr J. Gordon Chan 619 Lower Plenty Road Department of Nuclear Medicine, Yallambie VIC 3085 Austin & Repatriation Medical Centre, Heidelberg VIC 3084 Tel: (03) 9433 2211 Tel: (03) 9496 3336 Fax: (03) 9432 1835 Fax: (03) 9457 6605 email: john.baldas@arpansa.gov.au email: gordon.chan@petnm.unimelb.edu.au

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President’s Report WELCOME to this issue of the Gamma Gazette put together with assistance by my home branch of NSW. Many things are happening within and related to the Society at present and I will try and give you an update on some of these exciting developments.

Some members of the ANZSNM leadership and I had a profitable meeting with the SNMMI President and its executives at the SNMMI Annual Scientific conference in Baltimore in June 2015. The bilateral relationship is growing stronger and the President of the SNMMI will be attending our annual conference in Rotorua with his Technologist counterpart. The ANZSNM Scientific Advisory Panel has again secured two dedicated CME sessions for ANZSNM to present at the SNMMI 2016 in San Diego. The two sessions will focus on lung imaging and melanoma, in which our Society has shown leadership and have attracted a large audiences at these sessions in the past. This tradition has been in place since 2013 and is continuing. The Society is considering applying for a third CME session to speak at the categorical session with a focus on Ga-68 PET and its useful application in NET & prostate cancer imaging. ANZSNM will be engaged with the President and the Executives of EANM at the EANM Conference in Hamburg in October this year. The major focus of the joint meeting will be to explore the possibility of exchange of Scientists/Medical graduates between Europe and Australia and get access to e-Proceedings of EANM for ANZSNM members.

As ANZSNM now holds the Presidency of the WFNMB (World Federation of Nuclear Medicine & Biology) between 2014 and 2018, there are several constructive initiatives being undertaken by the new WFNMB leadership.

The ANZSNM’s IRC (International Relations Committee), which is the integral link to the WFNMB will be instrumental in expanding global nuclear medicine activities, particularly in education and training activities in many new emergent world regions, and in particular in the Asia and Oceania region, where Nuclear Medicine and Molecular Imaging are expanding very rapidly.

Professor Andrew Scott has undertaken initiatives with ALASBIMN (Latin American Societies) for similar activities in South America. As part of the Nuclear Medicine Global Initiative (NMGI), the WFNMB and SNMMI are working on a project on Radiopharmaceutical Access and Availability, which is nearing the data collection phase.

The plan is to seek information from all available countries on the availability of Radiopharmaceuticals, the issues relating to access and availability (including regulatory, transport, cost, infrastructure, training etc), and thus enable strategies for addressing a fundamental issue for the practice of Nuclear Medicine worldwide. The outcome of the project will have data that has not been generated in the past and it will be a useful reference document.

The forthcoming annual conference of ANZSNM-2016 in Rotorua, in New Zealand is shaping up very nicely with the participation by the President of SNMMI, Dr Hossein Jadvar, and Dr Diana Paes, the Head of Nuclear Medicine Section at IAEA (International Atomic Energy Agency, Vienna).

The prominent overseas speakers include: • Prof Giuliano Mariani MD, Professor and Chief of Nuclear Medicine Director of Post Graduate Specialty of Nuclear Medicine, University of Pisa, Italy; • A/Prof Gilmore David MS, CNMT, Associate Dean, Undergraduate Academic Affairs Program Director of Medical Imaging Programs Regis College, Boston, USA; • Dr John Humm PhD, Medical Physicist Memorial Sloan Kettering Cancer Center, New York, USA; • Prof Richard L. Wahl, M.D., FACR, Elizabeth E. Mallinckrodt Professor Head: Department of Radiology Director: Mallinckrodt Institute of Radiology Washington University School of Medicine, St Louis, USA. You can be certain that these excellent speakers will provide updates on the latest developments in Nuclear Medicine. Their participation will continue to improve the bilateral relationships between ANZSNM and overseas associations. Australian speakers will complement the overseas speakers to provide a high quality education & conference in Rotorua. The local organising committee led by Dr Sue O’Malley and Dr Darin O’Keeffe has been working hard to make it a grand success in New Zealand. The conveners are also aware of the variety of options involved in travelling to Rotorua so be on the lookout for regular updates on transport options to maximise your experience for your trip to a very special part of New Zealand. The Professional Organising committee, Jo Kelk and her team, will offer the best service to the conference. I am sure it is going to be a grand occasion and I wish to see you all attend the premier annual event in Rotorua April 22-25, 2016.

The ANZSNM has joined forces with the AANMS in a number of recent developments, such as the clinical trials group, ARTnet, and a Radiopharmaceuticals Licensing and Registration working party to enhance dialogue with government, and we should see this continuing into the future. This has recently been emphasised by the signing of an agreement between ANZSNM and AANMS that acknowledges that the ANZSNM’s Annual Scientific Meeting is also the AANMS’ premier annual scientific event. The options are also being explored to establish a continued on page 12

7

Branch News ACT ON September 10 the ACT Branch enjoyed an informative meeting at the Radpharm premises in Belconnen.

Two Radpharm award entrants were given the opportunity to present their case studies. Megan Stirrat gave her presentation on “The role of Nuclear Medicine in diagnosing Paraganglioma with SDHB Mutation” and Colin Mercer imparted his knowledge on imaging sublingual thyroid glands. The branch members voted and Megan Stirrat was awarded the Radpharm prize. Well done to both entrants!

Following these presentations Steven Farrell from Radpharm presented our group with information on the GMP processes involved in the manufacture of radiopharmaceuticals. Steven then led a tour of the manufacturing facility which demonstrated the various environments that the radiopharmaceuticals are prepared in. Everyone left satisfied that the QA procedures employed by Radpharm ensure the safest and most scrutinised radiopharmaceutical products available on the market.

Our next event will be our annual breakfast meeting just before Christmas. I look forward to seeing you all there.

Sharon Mosley, ACT Branch NEW SOUTH WALES FOLLOWING the cancellation of the April 2015 branch meeting due to weather conditions, the meeting was rescheduled for Wednesday August 19 at Royal North Shore Hospital given as a ‘Green Lecture’ presented by Dr Hojjat Ahmadzadehfar on “SPECT/CT in Benign and Malignant Diseases”. This was very successful with the speaker giving the lecture live from Germany to those in the meeting room and the presentation being recorded for future CPD. This technology, if available will enable members to actively participate in the lecture remotely, making CPD more accessible for rural and non-metropolitan members. We hope to work with the secretariat to provide similar meetings in the future and make the technology available to other branches.

The final ‘Christmas’ meeting for 2015 will be held on Wednesday November 19 at the Siemens Office North Ryde with a ‘The Year in Review: Highlights of 2015’ presented by a group of experts followed by the AGM then dinner and a quiz.

The NSW branch has several new members that are listed below. If you have an interest in joining the committee please contact the branch chair or any other member of the committee.

Dr Elizabeth Bailey (chair)

Prof Dale Bailey

Dr Eva Wegner

Mr James Player

Mr Andrew Cluff

Ms Linda McCarthy The branch would like to acknowledge and thank Ms Tracey Trevaskis, who resigned as chair of the NSW branch at the end of July 2015 for her amazing work and dedication to the society and its members.

Elizabeth Bailey, Chair NSW branch NEW ZEALAND OUR Annual Branch Meeting was held in Auckland in early September. Titled Magma and Molecular Imaging, the weekend meeting opened with a very interesting talk from Shane Cronin on “Auckland City of Volcanoes”. After an explosive and enlighting start we settled into fantastic talks from both invited speakers and branch members.

Our prize winners were: Radpharm Award: Divya Trichy “In-vivo Besilesomab Labelled Leucocyte Imaging” Paul Orr Award: Dr Berry Allen “Is Quantitative Dynamic SPECT a Reality?”

Cyclotek Pharmaceuticals Poster Prize: Erin Kelly “Predicting the Unpredictable: A case of hereditary Paraganglioma” Retirement of Dr Kevin Smidt It is with a real loss to our Nuclear Medicine Community that Dr Kevin Smidt is announcing his retirement after 40 years of service to Mid Central DHB. Kevin has been a steady force in this region for many years providing a reliable and sound service to many patient’s over his years at Palmerston North Hospital.

Kevin has also supported the Nuclear Medicine service at Wairau Hospital, and has been able to report remotely for colleagues taking leave to keep the Nuclear Medicine service rolling.

Aside from his undoubted good clinical skills, he was able to get installed a modern Siemens 16 slice SPECT/CT camera which will set the department in a good position for some years to come.

However while this is all testament to his dedication and clinical skill, it pales compared to his commitment on the 8 Gamma Gazette November 2015

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Branch News

continued

dance floor. Kevin has been a dazzling figure on the dance floor at the NZ Branch meetings and Gala Dinner dance floor. Things are simply not going to be the same.

On behalf of all our members, I would like to formally thank Kevin for outstanding service and contribution over an incredible 40 years to our Nuclear Medicine Community.

Dr Sue O’Malley In other news from NZ, the first Ga68 generator is being installed in Auckland

by Mercy Radiology with the first patients being scanned in October. This is a fantastic opportunity of NZ patients who have currently had to travel to Sydney or Melbourne for scans.

Hot Science: “An Eruption of Isotopes” is the title of the 2016 Annual Scientific Meeting in Rotorua, 22-25 April 2016.

Dr Sue O’Malley and Dr Kevin Smidt.

Abstract submissions opened in October 2015, and a reminder for this will be sent out by the organising committee shortly. Book your conference leave, find some flights and come and join us in this fantastic part of NZ. www.anzsnm2016.com/ Pru Burns, NZ Branch Secretary QUEENSLAND AT the end of 2014 we had our final meeting for the year which was for the Queensland Radpharm presentations.

The meeting was sponsored by GMS. We had three entrants and our successful entrant was Ingrid Holmes from the RBWH. Ingrid went on to the Annual Scientific Meeting and was the winner!! Congratulations Ingrid.

We had several committee members step down from their positions. Co-secretaries Nikki Weinert and Kathy Roy, Treasurer Tale Liiv and Federal Representative LJ Michel. I would like to extend my thanks to all these girls who have made my job as Chairperson much easier over the past few years. A special thanks to LJ Michel who has been in her position for several terms.

Our new committee members are James Turner and Louis Gray who will fill the co-secretary roll, Emma Snow – Treasurer and Clare Radley is the new Federal Rep. I would like to welcome the new committee.

The first meeting of 2015 was held at The Prince Charles Hospital. The meeting was sponsored by Siemens. We would like to extend our thanks to our two speakers for the night, Dr Bruce Goodwin and Deborah Tout.

Our 2nd meeting was held at the Queensland Pathology Learning Centre and we had two guests’ speakers. Dr Emlyn Jones gave his Pioneer lecture from the Annual Scientific Meeting and Simon Critchley from Radiation Health talked to us about Use licence regulations. Thanks are extended to our two guest speakers. Meeting was kindly sponsored by Mallinckrodt Pharmaceuticals.

Our most recent meeting was at the PAH and our guest speakers were Dr Catherine Lucas and Dr Tom Huang.

Their talks were both entertaining and informative and we extend our thanks to them for giving up their time. The meeting was sponsored by Insight.

Our final meeting for the year will be held in November and will be our AGM and Radpharm presentations. We look forward to seeing lots of interesting cases.

I would like to extend my thanks to the new committee of James, Louis, Emma and Clare who have all done a fantastic job in their first year of the job. Looking forward to a great year in 2016.

Melinda Wilson, QLD Chairperson SOUTH AUSTRALIA THE SA branch of the ANZSNM has already had a variety of speakers address us this year.

Firstly we were lucky enough to have Prof Markus Schwaiger – the Director of Nuclear Medicine at TUM’s rechts der Isar clinic present after the Brisbane ANZSNM conference. He was very charismatic and obliging - in fact when asked how long his talk would be, his reply was ‘However long you would like it to be’. His passion for Nuclear Medicine and it’s role with complementary imaging modalities could clearly be felt. Though he had visited Australia previously, he had not held a Koala, so he was taken on a day trip to Cleland National Park where he made friends with our furry natives.

Secondly at our most recent branch meeting we had a presentation by Marianne Keller a National Imaging Facility Fellow at SAHMRI entitled ‘Pre-clinical imaging modalities at SAHMRI’. With SAHMRI (South Australian Health and Medical Research Institute) promoting SA’s research opportunities, it was fantastic to learn a little about how

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Branch News

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the machines we use every day in medical imaging are being used (albeit in shrunk down versions) to help with research both in our state and nationally.

Holly Turner, SA Branch Chairperson VICTORIA/TASMANIA 2015 has been another busy year for the ANZSNM in Victoria and Tasmania.

The branch kicked off its annual Continuing Education activities early with Kim Williams annual January pilgrimage to Melbourne. Prof Williams’ presentation “Update in Nuclear Cardiology: Highlights of ASNC 2014” was of great interest highlighting pertinent trends and emerging uses for Nuclear cardiology to over 50 attendees.

CPD and Education events have been the main focus of the branch in 2015. We hosted two of the ANZSNM Conference Invited speakers in April. Pre conference we were treated to an excellent presentation by Prof Frank Roesch who spoke about 68Ga, the state-of-the-art 68Ga-radiotracers and the impact of 68Ga on Theranostics.

Post conference, Prof Michael Knopp presented on “Refined concepts for PET/CT acquisition” and his groups’ first experience with a digital detector PET system.

The Annual Day Seminar was held on Saturday October 24 at the Crowne Plaza.

Other projects undertaken by the branch in the last six months focussed once again on the promotion of Nuclear Medicine and in particular Nuclear Medicine Technology and Medical Physics as vocations. The ANZSNM is working in conjunction with the VSNMT and the Victorian Department of Health in promoting these career options and raising the profile of Nuclear Medicine in Victoria. The first event was The AGE VCE and Careers Expo held at Caulfield racecourse May 7-10. The branch will also have a presence at the 2015 STAVCON conference after the success of last year’s attendance. I would like to thank Cherann Edwards, Ailsa Cowie and the rest of the Nuclear Medicine promotions groups for their work in this area.

2014 and 2015 have been a time of significant change for the local committee with the resignation and retirement of several long serving members. I would like to thank them for all the work they have done over their many years of service. The branch welcomes new members, Kim Jasper, Lauren Dorn and Jessica Welch. They have been swiftly put to work as Office Bearers – Kim Jasper is the new Treasurer and Jessica Welch is the new Secretary.

Mary Anne Keady has taken over as Chair of the Vic/Tas Branch.

The branch would like to pay tribute to David Bell who recently retired from his position at Lantheus Medical Imaging. David has had a long and distinguished career in Nuclear Medicine in Victoria. He was Chief Technologist at Queen Victoria Medical Centre, Monash Medical Centre and Maroondah Hospital prior to his tenure at Lantheus.

David also contributed greatly to the profession over the years through involvement with VSNMT and ANZSNM committees and was a friend and wise mentor to many Victorian technologists. We wish him well.

Melinda Wilson, QLD Branch Chairperson WESTERN AUSTRALIA THE WA branch held our annual workshop this year at the University Club at UWA on Saturday August 1. The day was a wonderful success and we had approximately 70 attend. The day focussed on the genitourinary system and was well covered by our invited speakers from both a nuclear medicine and non-nuclear medicine perspective. Thank you to our speakers for such varied and interesting content; Dr Siobhan Ng, Dwayne Scott, Dr Andrew Patrikeos, Dr Basil Sclanders, Assoc. Professor Justin Vivian, Dr Colin Tang, Assoc. Professor Ros Francis, Dr Nelson Loh, Peter Peralta, Matthew Patterson, Lauren Hurn and Dr Liz Thomas. The hot topic for the day was 68Ga-PSMA and was discussed thoroughly in a panel discussion just before lunch. Not to be forgotten, Dr Nelson Loh gave his famous post lunch quiz which was enjoyed by all. Thanks to the committee who organised the event and the sponsors; GE, GMS, Siemens, Ansto and Bayer who made it possible.

We held our annual Radpharm Award night recently on September 22 at Princess Margaret Hospital. We had three excellent entries this year; Cassandra Koudela, Eleni Srestha and Julie Crouch. In the end, our winner was Julie Crouch from Oceanic Medical Imaging presenting “Hyperparathyroidism: A Full House!” Congratulations Julie and good luck in Rotorua next year!!! The night ended with a very interesting talk from Dr Al-Ogaili on cancer immunotherapy which included some insightful information on new treatments that may impact on oncologic scan appearances in PET. Big thanks to GMS for sponsoring the evening.

Our AGM will be held on Tuesday November 24 at SKG and will be our last branch meeting for the year. We look forward to seeing you all there.

Finally, on behalf of the committee, big congratulations to our Treasurer Stephanie O’Donnell, who has welcomed a beautiful baby boy into the world!

Amy Evans, WA TSIG Representative

10 Gamma Gazette November 2015

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Special Interest Group News TECHNOLOGISTS THE ANZSNM Technologist Special Interest Group has a strong focus on continuing professional development and we are currently working on several projects to increase the range and type of CPD activities provided to nuclear medicine professionals. The TSIG-committee has allocated members to be responsible for specific CPDrelated enquiries, including CPD course/activity approval (James Green ACT/ Jacqueline Brague NZ), CPD audit (Amy Evans WA), leave requests (Marcia Wood Vic/Tas) and general CPD-related questions to the secretariat (secretariat@anzsnm.org.au).

The TSIG will hold its very first webinair in early November, with the date and speaker to be confirmed on the ANZSNM website. Starting 2016, there will be 3 webinairs held per year covering a broad range of topics. If you have a suggested topic for a webinair please contact your local state representative. We have also been reviewing and developing a range of PET related topics that will be made available on-line as a way for members’ to gain expertise in PET/CT theory and clinical practice. At this stage, it should be available early 2016 and can be used for CPD. The ANZSNMT are also working closely with the University of Queensland to develop an MRI course for nuclear medicine technologists and other allied health professionals with a focus on PET/MRI. The annual TSIG symposium for 2015 was held in Hobart on Saturday June 20 at the Woolstore as part of the winter solstice “Dark MoFo’ Festival. There were approximately 65 attendees with a wide variety of topics presented focusing predominantly on Molecular Imaging using SPECT/CT and PET/CT and new radiopharmaceuticals. A great day was had by all and we would like to thank the sponsors for their ongoing support. The TSIG symposium for 2016 will be held in Canberra at the National Press Club of Australia on Saturday 23rd July with a theme “A Capital Calibration’. A call for abstracts and earlybird registration opens 29th February, so ‘save the date’.

The Annual Scientific Meeting will be held in Rotorua New Zealand at the Energy Events Centre April 22-25, 2016 and the Technologist Symposium is scheduled for Saturday April 23 with invited technologist speaker A/Prof David Gilmore from Regis College Boston. The TSIG and NZ-LOC will also be hosting CE sessions throughout the scientific program using local invited speakers presenting on their area of expertise. Abstracts and registration are due to open October 2015, so it’s time to start thinking about preparing your abstracts.

The Mallinckrodt award winner for 2014, Mr Scott Evans from Westmead Hospital presented his award winning presentation at the Society of Nuclear Medicine and Molecular Imaging (SNMMI) annual meeting Technologist Symposium in Baltimore June 2015. Congratulations to Scott for representing the high calibre of work undertaken

by Australian Nuclear Medicine Technologists. The winning entrant from 2015 will present at the SNMMI-TS meeting in San Diego California June 2016.

I would like to thank the TSIG committee members for their dedication and support in 2015 and look forward to working with you again in 2016. Wishing you all a happy Christmas and fantastic New Year, keep safe and relax.

Liz Bailey Chair ANZSNMT

President’s report

continued

Continued from page 7

Radionuclide Therapy multi-disciplinary group within the framework of the society. I am delighted to say again that I am privileged to work with a team of dedicated members in the Federal Council, and with the Secretariat, and appreciate their support in all facets of running the activities of the society.

I would greatly appreciate to know how we can improve the services provided, as we expand further into the digital world. The ANZSNM has continued to work closely with the Secretariat and improve the new website for the society. Federal Council is progressing to incorporate all essential information: to perform many tasks such as membership renewal, co-ordinate and publicise SIG activities, deliver CME and accreditation-related activities, and disseminating information through its on-line presence as well as in Gamma Gazette. The website has helped the financial membership to reach around 980 and growing.

Prof. Vijay Kumar President ANZSNM vijaykumar493@gmail.com

12 Gamma Gazette November 2015

CPD Update CONTINUING Professional Development (CPD) has become one of the main focuses of the TSIG over the past few years, building on the initial CPD program set in place previously by the now defunct Accreditation Board of the ANZSNM. While accreditation is no longer a function of the ANZSNM, the CPD program continues on, and is a recognised program by the Medical Radiations Practice Board of Australia (MRPBA). This is a reflection of the quality of the program in place when MRPBA registration came into effect. It also means that our program must conform to certain standards and be able to prove that we comply with them.

Some members have been audited recently by the ANZSNM for CPD records. Although the MRPBA is performing auditing for registration purposes, the ANZSNM also need to perform auditing to prove we are conducting our program in accordance with the MRPBA standards. Approximately five percent of our members will undergo auditing each year as part of our ongoing commitment to providing a recognised program.

The new website has a CPD area with increased functionality to allow for recording the reflective practice components required by the MRPBA and to assist in ensuring that audits are as easily achievable formembers.

We also recommend that members accrue more than the minimum requirements, in the event that some hours are not approved.

The granting of “Leave of Absence” from the CPD program has also become another important function.

Members may apply to take up to 12 months leave of absence for reasons such as family leave, extended illness or other personal reasons. This exempts the member from the need to accrue CPD points up to a maximum of 20 hours (12 months) once during a CPD triennium. Other time frames are calculated on a pro-rata basis. The requirement to accrue 20 hours per year for the other two years remains, and no reduced activity in these years is possible. It is important that people wanting to take a leave of absence apply at the start of the period of leave, as again, this is tied to our program recognition. Leave will not be able to be granted retrospectively. It is also important that members are aware that they also need to inform the MRPBA of any leave of absence from CPD. Forms for this are available from the secretariat.

Finally, we are able to approve programs from other providers as activities that our CPD will recognise – Appellation. We would encourage members to notify the TSIG via the secretariat if there are activities we could extend this to. This may include educational offerings from vendors. Having activities already approved helps take the uncertainty out at audit time.

Marcia Woods and James Green ANZSNMT Committee

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Workshop Internal Dosimetry Assessment in Nuclear Medicine

Australian Nuclear Medicine at Indonesian Dosimetry Workshop

Participants on Day 1 of the course.

Members of the Indonesian Society of Nuclear Medicine and nuclear scientists from BATAN (the Indonesian equivalent of ANSTO) organised a two-day workshop in the city of Bandung, West Java.

August 26-27, 2015 DR Price Jackson (Peter MacCallum Cancer Centre) and I were invited to participate as joint course directors and lecturers. The meeting was sponsored by the Indonesian government and the IAEA. Over the two days we discussed methodology for calculating dose to tissues and organs from radiopharmaceuticals for both diagnostic imaging and therapy and applications. Indonesia has recently starting producing its own 177Lu at the Serpong reactor just outside of Jakarta. Local lecturers discussed clinical applications of radionuclide therapies and the use of Monte Carlo modelling of dose distributions in vivo. Bandung is the capital of West Java and is situated in the mountains approximately 150km east of Jakarta. It is traditionally the home of nuclear science in Indonesia and the birthplace of the field of Nuclear Medicine in Indonesia. It has a long tradition in education and training residents and registrars in Nuclear Medicine.

The immediate past-president of the Indonesian Society of Nuclear Medicine, Dr Hussein Kartamihardja, who undertook part of his training in Sydney, is the current head of the Department of Nuclear Medicine at the Dr Hassan Sudikin Hospital and Padjadjaran University Medical School where the course was held.

Also in attendance was the former Director of Nuclear Medicine and the man who established Nuclear Medicine in Indonesia, Professor Johan Masur. The department has a PET/CT scanner and is expecting a cyclotron to be installed within the next 12-18 months.

It also boasts state-of-the-art SPECT/CT imaging facilities.

Approximately 65 attendees participated in the meeting.

It was the second time that I have been fortunate enough to visit Bandung, having taught a course there on behalf of the Department of Foreign Affairs and Trade in 1988. Australia has had a significant input into the development of Nuclear Medicine in Indonesia, our closest northern neighbour, and the most populous Islamic nation in the world with a population of over 250m people.

14 Gamma Gazette November 2015

Price Jackson (2nd from left) and scientists from BATAN standing on top of the 2MW Triga Mark III research reactor in Bandung. The reactor first achieved criticality in 1964.

Many Nuclear Medicine professionals from Indonesia have trained in Australia and we have maintained close links with them over many years now. Indonesia now has a number of PET centres with cyclotrons and state-of-the-art radiopharmaceutical production facilities. During the course, Price was invited to visit the Bandung reactor which had undergone an upgrade and was preparing for hot testing on the day of his visit.

It is activities such as this that we are seeking to expand and promote as part of the World Federation of Nuclear Medicine and Biology program culminating in to the World Congress in Melbourne in 2018. The increasing availability of suitable IT infrastructure in neighbouring countries such as Indonesia ought to make us rethink alternative ways for us to contribute to further education and training in the neighbouring countries of our region and beyond.

Prof Dale Bailey Royal North Shore Hospital, Sydney

Significant milestone for

Australia’s new Nuclear Medicine manufacturing plant AUSTRALIA is one step closer to securing Australia’s supply of nuclear medicine and becoming a global, high-end manufacturer of these lifesaving products, as a significant construction milestone was recently met on the $168 million ANSTO Nuclear Medicine (ANM) facility.

The new facility, based at the Lucas Heights campus of the Australian Nuclear Science and Technology Organisation (ANSTO), is now above ground with large areas of the building waterproofed and the interior fit out on track.

With this development, ANSTO approaches the target of tripling production of molybdenum-99 (Mo-99), which is used in hospitals and medical centres to make Technetium-99 (Tc-99m), the most widely-used radioisotope in nuclear medicine worldwide.

ANSTO has been the primary supplier of Mo-99 to Australia, but the global supply has come under threat in recent years because of the closure of ageing research reactors worldwide.

Currently ANSTO produces around 10,000 patient doses of nuclear medicines per week, which is distributed to more than 250 hospitals and nuclear medicine centres across Australia, as well as shipping product internationally.

The current world demand for Tc-99m is estimated to be approximately 40 million patient doses per annum. Once fully operational, Australia’s new Mo-99 manufacturing plant will enable ANSTO to significantly increase its production capabilities and supply up to 25-30 per cent of global demand.

ANSTO CEO Dr Adi Paterson said the ANM facility is an example of how Australia is helping boost the worlds’ access to reliable sources of nuclear medicine.

“To give an idea of the project scale – this year ANSTO celebrated the fact that since 2008 our existing facility has produced four million doses of nuclear medicine for domestic supply,” said Dr Paterson.

“Once this facility is operational and running at full scale – we estimate we will be producing more than 10 million doses a year, which is more than a quarter of the world’s demand.”

Members of the ANM Board standing in front of the construction site for the new Mo-99 production facility at Lucas Hts. From left to right: Con Lyras, Doug Cubbin, Sarah Ballantyne, Greg Santamaria and Sarah Pearson.

15

Online Registration Now Open – Register Now at www.anzsnm2016.com You are warmly invited to register for the ANZSNM 2016 Annual Scientific Meeting.

The Organising Committee has been working hard behind the scenes to create an exceptional event for the Nuclear Medicine community – including an outstanding Scientific Program, as well as a range of social functions and family-orientated activities for yourself (and your family) to choose from.

As the ANZSNM ASM for 2016 is taking place over ANZAC weekend (Monday 25 April is a public holiday in New Zealand), we strongly recommend that you register early and arrange any transport and/or flights as needed, to ensure that you get the best possible rates and convenient travel times.

To assist both international and domestic travellers in getting to Rotorua, the Organising Committee is providing several complimentary return bus connections from the International Terminal at Auckland Airport to Rotorua. You have the ability to book any of these bus connections via the online registration process – further details about connection dates and times, can be found on the meeting website.

Please review www.anzsnm2016.com for further information about the Scientific and Social Programs. If you have any questions or require assistance during the registration process, please contact the Conference Managers anzsnm@outshine.co.nz Important Dates • • • •

Early bird registration closes 6 March 2016 Standard registration closes 3 April 2016 Hotel rooms and conference rates will be held until 20 March 2016 Abstract submissions close 29 January 2016

Abstract Submission Now Open The Organising Committee would like to invite abstract submissions for oral and poster presentations at the upcoming ANZSNM ASM 2016. Submissions from all disciplines of Nuclear Medicine are invited for presentation.

To be selected to present a paper at the ASM, you are required to submit an abstract via the website. All abstracts must be submitted electronically, and uploaded in the system in a Microsoft Word .doc or .docx format. Abstracts will be blind reviewed, and must not exceed 300 words.

Please visit the Meeting Website www.anzsnm2016.com to review submission instructions.

Abstract Awards

There are a number of Awards available for the 2016 ANZSNM ASM, including; • RADPHARM Case Presentation Award • Mallinckrodt Award • GMS Poster Award • Gammasonics Abstract Award • AANMS Registrar Research Award To apply for the above Awards, except the AANMS Award, you must be a financial member of the ANZSNM for at least six months at the time of presentation at the ANZSNM ASM. You will be required to supply your ANZSNM membership number during the online submission process.

Full award rules can be viewed on the Society Website www.anzsnm.org.au

Thanks to our Confirmed Sponsor Gold Sponsor

Silver Sponsor

Diary dates Email the Production Editor at the Secretariat at secretariat@anzsnm.org.au to list your upcoming conference and meeting dates on the diary page.

2015

2016

15-16 November Advanced Workshop in Thyroid and Parathyroid Imaging North Shore Hospital, Sydney, NSW, Australia www.anzsnm.org.au/events/event/advancedworkshop-thyroid-and-parathyroid-imaging

12 February Physics Special Interest Group Symposium “Techniques in NM functional imaging and image reconstruction” University of Sydney, NSW

18 November ANZSNM SIEMENS CHRISTMAS Branch meeting Siemens Offices, 160 Herring Rd, Macquarie Park, NSW 2113 24 November WA Branch AGM SKG (SJOG) Subiaco 25 November SA Branch AGM & Quiz Night Belgian Beer Café, Adelaide, SA

22-25 April 2016 ANZSNM Annual Scientific Meeting Rotorua, New Zealand www.anzsnm2016.com 23 July 8th Annual TSIG Symposium National Press Club, Canberra, ACT

2018 20 – 24 April 2018 WFNMB 2018 Congress Melbourne, Australia

17

ANZSNM Annual General Meeting 2015 MINUTES Date: Sunday, 19th April 2015 Time: 12.10am Venue: Plaza Auditorium, Brisbane Convention Centre, Brisbane 1. ATTENDANCE 75 members present which under the Constitution was a quorum.

2. APOLOGIES Clayton Frater, Douglas Howarth and Frederick Khafagi were the notified their absences 3. MINUTES OF THE PREVIOUS MEETING The minutes of the previous AGM at the Adelaide Convention Centre on 27th April, 2014 were accepted as a true record.

4. BUSINESS ARISING FROM THE PREVIOUS MINUTES No items were raised.

5. REPORTS Reports were presented to members on topics by the presenters indicated.

5.1 President’s Report: Prof. Vijay Kumar – The development of a new ANZSNM website by the Secretariat provides a comprehensive platform for the Society’s activities including a more efficient membership renewal process; as of now there are > 800 financial members.

– The World Federation of Nuclear Medicine and Biology (WFNMB) Conference to take place in Melbourne in 2018, planning for which was being coordinated by Drs Sze Ting Lee, Scott and Kumar. Between now and 2018 the ANZSNM will be responsible for directing the WFNMB to expand global nuclear medicine training and education activities – The 2015 Annual Conference includes several prominent international and national speakers, the attendance of the Presidents of SNMMI, SNMMI-TS and ARCCNM and > 400 delegates, this ensuring the overall success of the meeting. The President expressed his thanks to the meeting organisers, Dr Joseph Wong and Lyndajane Michel.

– The ANZSNM continues to work with the AANMS on a number of initiatives including ARTNet, and the Radiopharmaceutical Licensing and registration working party to enhance dialogue with government.

– The award of Life Membership to Professor John Morris: in support Dr Dale Bailey summarised Professor Morris’s career and his contribution to nuclear medicine in Australia.

– The President first thanked Dr. J Wong, Lyndajane Michel and the 2015 Conference Organising Committee, together with all members of Council and the Secretariat for their continuing contribution to the activities of the Society.

There were no points of discussion on the President’s report.

5.2. Treasurer’s Report: Dominic Mensforth – A summary of the audited accounts for 2014 was visually presented and compared to 2013 which showed a deficit of $71,370; the full accounts were to be available on the ANZSNM website.

18 Gamma Gazette November 2015

– A similar deficit to 2014 is likely to be incurred as budget for 2015 but the aim is to achieve a balanced budget by 2018.

– This will be achieved through: i. Increases in memberships fees as agreed at 2014 AGM ii. Increased membership numbers through additional

offerings such as improved CPD iii. Reductions in costs of various activities including Council

and Annual Conference iv. Budget for Annual conferences to generate a substantial surplus.

– There were no points of discussion.

5.3. TSIG Report: Dr Elizabeth Bailey – The PDY program ceased on 31st March 2015 with AHPRA now taking over this function as part of professional registration.

– The Society would continue to operate the Mentor program to support new NMTs. – An ECG course was being planned with first enrolments in Jan 2015.

– The annual TSIG symposium would take place in Hobart on 20th June; the program was being finalised with sponsorship of approximately $5000.

– A CPD sub-committee had been formed to oversee CPD activity approvals, assist the secretariat with queries and undertake CPD audits as required by the MRPB. – Plans are to hold 2 webinars per year as part of a new education initiative.

– The 2014 Mallinckrodt award winner will present for the first time at the SNMMI-TS 2016, Baltimore. The reciprocal award to attend the ANZSNM ASM 2016 will be presented to the best oral presentation at the SNMMI-TS. – A joint session of the ANZSNMT & SNMMI-TS will take place SNMMI 2016 in San Diego, topic yet to be confirmed – A joint session of the ANZSNMT & EANM-TS is still being negotiated.

In a question from Dr Andrew McLaughlin about why ANZSNM was not continuing the PDY program, Dr Bailey answered that this was not an option under the registration arrangements.

5.4. AANMS: Dr Sam Berlangieri – Collaboration continued between the ANZSNM and AANMS in relation to training and CPD – In 2015, several courses were run including Cross-sectional anatomy, a 2nd Masterclass and a Basic Sciences Course for all nuclear medicine trainees.

– Interaction with Government took place through various bodies including DoHA where there was discussion of the possible impact of co-payments on nuclear medicine practice.

– In relation to MSAC, concern was expressed about the inability to get reimbursement approval for new nuclear medicine applications.

5.5. Physics SIG: Dr Darin O’Keeffe – The Physics SIG AGM held on Saturday 18 April 2015; minutes were to be available on the ANZSNM website in due course and Daniel Badger elected as Chairperson and Andrew Chicco as Secretary/Treasurer.

– Thanks were extended to Chithra Sathiakumar (Treasurer) and

–

– – – –

Sylvia Gong (Secretary) for many years of service on the SIG committee.

A successful symposium held at the University of Sydney on Friday 13th February - “Back to the future: Functional imaging in radiation oncology”; Thanks to Dale Bailey and Chithra Sathiakumar for helping to organise it, and to presenters for their contribution; also thanks to sponsors who make these symposia financial viable; presentations included an impressive remote presentation by Dr Stephen Bowen, University of Washington, on “PET/CT & SPECT/CT in Radiation Therapy” and such modes of presentation should be considered for future meetings.

The next symposium is on Friday 12th February 2016 at the University of Sydney, topic TBD. Feedback was requested on level of interest of “Column8” columns in Gamma Gazette.

Physics SIG Chairperson thanked all those people who supported him during his four year term as Chair and on Federal Council.

The President thanked the outgoing SIG Chairperson for his contributions.

5.6. Technical Standards Committee (TSC): Darin O’Keeffe.

- The new committee members are Nicholas Forwood (NSW) and James Green (TSIG); representative from Queensland still needed.

- Currently five main projects within TSC: i. Dose calibrator minimum quality control schedule – nearing completion. ii. Minimum quality control requirements for gamma cameras

– adopted by the Federal Council, but still waiting on

supporting guidelines document. iii. Software phantoms and clinical software validation –

stalled but regrouping. iv. Paediatric administered activity working party –on-hold

awaiting publication of Part 2 of the Nuclear Medicine

Global Initiative whitepaper on paediatric administered activities. v. In-house production of radiopharmaceuticals – working

party currently being formed; terms of reference are to

review “regulatory, technical, legal, and ethical implications

of the in-house synthesis of radiolabelled compounds,

especially for PET and radionuclide therapy applications,

and the staff who are qualified to undertake such operations”.

5.7. Radiopharmacy SIG: Report read by Prof. Vijay Kumar on behalf of Dr Doug Smyth – Progress is continuing with the registration of Qualified Radiopharmaceutical Scientists by the Professional Standards Board of ACPSEM. – A Workshop will be held in Sydney in May to finalise the program and will be supported by ANZSNM. – A Radiopharmaceutical Scientists Symposium will be held in Sydney in 2015 on the expanding area of metal-based radiopharmaceuticals.

– The Radiopharmaceutical SIG is working with the Technical Standards SIG to investigate the regulatory and quality assurance issues around the preparation of Ga-68 and Lu-177.

– –

– – –

Committees to ensure consistency in meetings and assist with choice of speakers, themes and named lectures The 2017 ASM will take place in in Hobart with Barry Ellison as the Chair of the Local organising committee.

Research awards were awarded in 2014 (4 applicants) to Drs Kenny Sek & Ros Francis and in 2015 (3 applicants) to Dr Peter Kench; applications are being called for 2016 and sponsorship is being sought as part of the general effort to reduce costs.

Council was considering the introduction of a Distinguished Achievement Award which was different to Life membership.

Discussions are continuing with AANMS on the formation of a Radionuclide Therapy Group.

Expressions of interest have been called for new SIG and Branch Representatives to SAP.

6. FORTHCOMING CONFERENCES 6.1. Rotorua 2016: Dr Sue O’Malley (Co-convenor) - The next conference is in Rotorua - 23-25 April 2016 - The PCO employed, is the same as in 2004 and 2010 in New Zealand.

- The theme - “an Eruption of isotopes”; secondary theme “Not just Numbers: The Evolution of Quantitative Nuclear Medicine - There were four invited speakers confirmed Pre-conference symposium worked out and timetabled - The Welcome was to be allocated to Friday night - There is a change in sponsorship expectation along with a transition from paper to electronic programmes and the like.

6.2 WFNMB International Relations Committee (IRC):

A/Prof. Sze Ting Lee – Planning has commenced for 12th WFNMB Congress in Melbourne, 20th to 24th, 2018, anticipated to involve over 2,000 attendees; will be combined with ASM of ABNZSNM. – WFNMB lead by – Sze Ting Lee, Andrew Scott, Vijay Kumar – and they are meeting to select a PCO in May/Jun 2015.

– IRC activities include meetings with leadership of major overseas NM societies, and planning new initiatives in advocacy, technical standards, teaching and quality programs.

– Global Dose Optimization initiative, through the active involvement of Dr Darin O’Keeffe, gratefully acknowledged at SNMMI. 7. COUNCIL MEMBERSHIP CHANGES The President expressed his thanks to retiring members Lyndjane Michel and Darin O’ Keeffe and welcomed their replacements to Council – Clare Radley and Daniel Badger respectively.

8. LIFE MEMBERSHIP TO RETIRED PROF. JOHN MORRIS Prof Bailey read to the meeting the recommendation that was used by Council in conferring Life Membership of the Society to Professor John Morris.

9. BUSINESS WITHOUT NOTICE There was no business without notice. The meeting was closed by the President at 1.00 PM.

5.8. Scientific Advisory Panel – Prof. Dale Bailey – The SAP continues to liaise with Local Conference Organising 19

Financial statements presented to the 2015 AGM of – Australian and New Zealand Society of Nuclear Medicine Limited

20 Gamma Gazette November 2015

A full financial report is available on the ANZSNM website anzsnm.org.au

21

Cardiac Imaging

word search

By Pru Burns, Pacific Radiology

A L B B B Z C B M K H G S D S A S W A D F G H Y T R E O D B T E T R O F O S M I N U F E T E F C B N M L K S D I Q L Q G L J G H Y N J C T F E L D A X C D E R T R H R P T I H T D G E W T Y C E C G U N O E L K F R T Y U M G O I G P D E F E C T C U I Y A S T U N N I N G W Y O A G M O Z S P L R O P R P Y H V P L X T R D T P D U H U F D L P V R T O S E S T A M I B I H I E F B V R Q D S G N R T I A S N U H F T R E D V U U B B S G T T U G T G C I X D E I R F A R S C R F O V P E R L D R M R I W W R F O V B N I T E I F O C B J K L E D T Y E S E O A R T E R I E S I A O L T P U F I H D S T G O G F I R S T P A S S Q Y T N L S L F T H K L Y U I P B

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22 Gamma Gazette November 2015

answer on page 25

A T H D N N N T L D G K E L

Australian and New Zealand Society of Nuclear Medicine Limited ABN: 35 133 630 029

Isotopes, Imaging and Identity – The History of Nuclear Medicine in Australia Book

Order and Payment Form ANZSNM Members:

AU $25 (inc.GST) Qty.

Name: Preferred mailing address please: Street: State: Postcode: Email: CREDIT CARD PAYMENT: Mastercard/Visa (Please circle) Expiry:

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Amount to be deducted $ Card Holder’s Name Card Holder’s Signature Email completed form to: secretariat@anzsnm.org.au CHEQUE MADE PAYABLE TO ANZSNM ANZSNM Secretariat PO Box 6178, Vermont South, VIC 3133 Tel: 1300 330 402 Fax: (03) 8677 2970 Email: secretariat@anzsnm.org.au

This document will be a tax invoice for GST when you make a payment

License to produce lutetium-177 n.C.A for clinical trials ANSTO has extended its production of radionuclides with an announcement that a license has been issued by the Therapeutic Goods Administration to produce Lutetium-177 noncarrier added (Lu-177 n.c.a.) for use in clinical trials.

Australian investigations and overseas trials have indicated Lu-177 n.c.a., combined with various molecules, has the potential to treat a variety of cancers, including neuroendocrine tumours. Though considered to be a rare tumour type, neuroendocrine tumours affect around 8000 Australians, with approximately 750 new cases diagnosed each year.

For those patients who may be suitable for this type of treatment, through clinical trials, access has been limited to Lu-177 n.c.a. from overseas supply.

Licensing represents the culmination of several years of work to design, construct, validate and obtain approvals for manufacturing this product in Australia.

GMP manufactured Lu-177 n.c.a. requires the irradiation of Ytterbium-176, followed by chemical separation processes. Lu-177 n.c.a is dispensed into vials and terminally autoclaved. The final product has the highest specific activity and radionuclidic purity. This non-carrier added product is also suitable for radiolabelling biomolecules such as peptides and antibodies that target tumours in the body. The half-life of 6.6 days facilitates the logistics of production, transportation and use at the clinic.

“ANSTO now has capacity to produce a reliable supply of a new investigational product that could lead to potentially-lifesaving cancer treatments,” said ANSTO’s Manager of Nuclear Business, Shaun Jenkinson.

“Evidence points towards it being an effective last line of defence – with clinicians telling us potential outcomes can include tumour shrinkage, with patients living longer and feeling better.”

Advantages • Specific activity of 4-5 times higher than Lu-177 c.a.

• Sterile, endotoxin tested • Significantly longer shelf-life • Security of supply through ANSTO’s additional arrangements • No contamination with long-lived Lu-177m (half-life 160.1 days) ANSTO is on track to commence initial production runs in November 2015.

It should be noted that Lu-177 is a radioisotope. It is an unregistered investigational medicine in Australia.

For more information please contact ANSTO Health customer service: Phone 1800 251 572 Email health@ansto.gov.au Web www.ansto.gov.au/ANSTOHealth

24 Gamma Gazette November 2015

Cardiac Imaging

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By Pru Burns, Pacific Radiology

By Pru Burns, Pacific Radiology

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25

SIR-Spheres (90Y-microspheres) treatment featured at ASCO meeting Chicago, USA May 2015 It is not often that a trial of radionuclide therapy features as a highlighted talk at the ASCO (American Society of Clinical Oncology) Annual Meeting but that is what happened in May this year when the results of the SIRFLOX clinical trial using SIR-Spheres were presented by Peter Gibbs, a Medical Oncologist from Melbourne. ASCO is one of the biggest medical conferences held annually with over 30,000 attendees. It has in recent years been held in Chicago.

SIR-Spheres are 90Y-labelled resin microspheres which are used to treat unresectable liver cancer (both primary and metastatic, figure 1) and, it is claimed by the manufacturer, Sirtex Medical (Sydney), to be the first cancer therapy wholly developed in Australia to be FDAapproved.

SIR-Spheres have tended to be used previously as a monotherapy or sometimes in combination with chemotherapy but the latter has not previously been studied systematically. The SIRFLOX study is the first report to look at SIR-Spheres as a first line treatment in combination with chemotherapy in metastatic colorectal cancer (mCRC).

Associate Professor Peter Gibbs, Co-Principal Investigator of the SIRFLOX study and Consultant Medical Oncologist, The Royal Melbourne Hospital, presented the results of the 530 patient SIRFLOX randomised controlled study, which open new possibilities for combining radiation targeted at liver metastases with first-line systemic treatment of mCRC. “We found that while liver tumours began to grow again after a median of 12.6 months in patients with mCRC who received only first-line chemotherapy, those who also received first-line treatment with SIR-Spheres 90Y resin microspheres had their liver tumours controlled for a median of 20.5 months. This finding matters a great deal because the liver is almost invariably the organ where colorectal cancer spreads to first. While half the patients initially diagnosed with colorectal cancer survive

thanks to surgical removal of the primary tumour before the disease has spread elsewhere in the body, liver metastases eventually cause the death of the majority of the remaining hundreds of thousands of patients each year whose tumours spread but are inoperable,” said Prof Gibbs.

To put the findings into context, the session discussant Professor Ricky Sharma, Clinical Senior Lecturer in Oncology, University of Oxford, UK indicated that in the period 2002-2014 the US-FDA had approved 71 drugs for the treatment of solid cancers, at a cost of many billions of dollars, and in this time the rate of progression-free survival had increased by 2.5 months and the median increase in overall survival was only 2.1 months.

Prof. Gibbs informed the ASCO audience that liver treatment response rates were significantly higher in patients who received 90Y resin microspheres in combination with first-line chemotherapy, which consisted of a FOLFOX-based regimen, with or without the addition of bevacizumab (AvastinÒ). “We observed a hepatic response rate of 78.7% in this group, compared to 68.8 per cent in the chemotherapy-only group. This was statistically significant, with a p-value of 0.042.

Moreover, the rate of complete responses in the liver of SIRFLOX patients who received SIR-Spheres 90Y resin microspheres, though relatively small at 6.0 per cent, was more than three times higher than the 1.9 percent complete response rate among the chemotherapy-only

Figure 1.

SIR-Spheres treatment. An example of PET scans in a patient with metastatic colorectal cancer with liver metastases treated with SIR-Spheres. The top row shows the baseline FDG PET scan demonstrating multiple lesions in the liver. The middle row shows the 90 Y microspheres imaged with PET the day after the treatment with good delivery seen to the FDG-avid lesions.

The bottom row shows the response achieved in the FDG PET scan just over 6 weeks after treatment. The majority of the lesions demonstrate a very good metabolic response.

26 Gamma Gazette November 2015

18

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SIR-Spheres (90Y-microspheres) treatment continued patients,” Prof Gibbs said.

“The statistical significance of this finding is very strong, with a p-value of 0.02.”

“The SIRFLOX trial gives us the data to validate the first-line use of selective internal radiation therapy, or SIRT, with SIR-Spheres 90Y resin microspheres in mCRC,” said Prof Guy van Hazel, Co-Principal Investigator of SIRFLOX and Clinical Professor of Medicine at the University of Western Australia, Perth.

“Until now, we have not had a randomised clinical study large enough to provide Level One evidence supporting first-line use of this treatment. This step forward matters to medical oncologists and their patients, because until the development of 90Y resin microspheres, there was essentially no place for radiation therapy in the treatment of liver tumours,” Prof van Hazel said.

“There was never a question that radiation would work in the liver, but the problem of administering the radiation in a way that spared healthy liver tissue from its effects prevented it from being an ‘equal partner’ with surgery and chemotherapy in treating mCRC, as it is in almost all other forms of cancer.”

SIRFLOX Principal European Investigator, Prof. Volker Heinemann, Director of the Comprehensive Cancer Center, University of Munich, Germany, said “Medical oncologists, particularly also at the community level, are only now beginning to recognise that treating liver metastases locally as well as systemically, is a very important clinical consideration in the effective management of this difficult-to-treat cancer, and may also open up the possibility of potentially curative liver surgery in some previously unresectable cases. The effect of 90Y resin microspheres on Progression-Free Survival (PFS) in the liver, as reported in the SIRFLOX study, is quite pronounced,” said Prof Heinemann. “Even in the absence of sufficient data to calculate an overall survival benefit or a significant finding for the primary endpoint of Progression-Free Survival at any site, the outcome of SIRFLOX suggests oncologists who treat mCRC may now wish to consider earlier use of 90Y resin microspheres than is presently the case, certainly among those patients whose metastatic disease has been diagnosed primarily in the liver. With SIRFLOX, the Level One evidence is there for every medical oncologist to see and to evaluate in their practice,” Prof Heinemann said.

According to SIRFLOX Principal U.S. Investigator, Dr Navesh K. Sharma, Assistant Professor of Radiation Oncology and Diagnostic/Interventional Radiology, University of Maryland Medical Center – the largest American clinical site for SIRFLOX, “With 530 patients, SIRFLOX is the largest randomised trial ever conducted that combined an interventional radiology procedure with chemotherapy in oncology. Physicians have been performing SIRT procedures with 90Y microspheres, in the US and around the world, for more than 10 years.

We have always felt that this procedure was a unique approach to deliver large doses of radiation to liver tumours, targeted in a way that spares healthy liver tissue,” said Dr Sharma. “It is important to observe that

in SIRFLOX, the clinical benefit that was observed came with an acceptable level of adverse events from adding 90 Y resin microspheres to first-line chemotherapy in mCRC. Oncologists, especially radiation oncologists, have traditionally been very cautious of irradiating large liver volumes because of the adverse effects associated with such treatments,” he continued.

“SIRFLOX has shown us, in an unbiased manner that, not only can we deliver high doses of radiation to the liver safely with this approach, but we can do so using concurrent chemotherapy. Concurrent chemo-radiation has been one of the most effective ways to treat cancer in general, especially those of gastrointestinal origin,” said Dr Sharma.

In a further indication of the potential clinical relevance of the combined chemo-radiation regimen studied in SIRFLOX, ASCO selected the SIRFLOX study results as one of just 71 of the several thousand abstracts reviewed for this meeting as a “Best of ASCO” presentation. “Best of ASCO” papers may be discussed in an ongoing cascade of official follow-up presentations that national oncology leaders will deliver over the coming months to medical oncologists in their countries who were unable to attend the ASCO Congress in Chicago.

SIRFLOX is the first of a group of three studies assessing the results of adding SIR-Spheres 90Y resin microspheres to first-line chemotherapy in the treatment of mCRC. The other studies are FOXFIRE, a UK clinical trial that completed enrolment in November 2014, and FOXFIRE Global, an international study that completed enrolment in January 2015. The results of the three studies, which together enrolled more than 1,100 mCRC patients, will be combined in a pre-planned assessment of the overall survival benefit of adding SIR-Spheres Y-90 resin microspheres to first-line chemotherapy for mCRC. The combined results are expected in 2017. The CoPrincipal Investigators of FOXFIRE are Prof Ricky Sharma and Dr Harpreet Wasan, Hammersmith Hospital and the Imperial College Trust, London, UK. It is always pleasing to see an Australian contribution to medical science achieve international recognition and this is certainly the case with the SIRFLOX trial. More work remains to be done in this domain, especially in understanding the relationship between the amount of radiation delivered and the response achieved (a “doseresponse” effect) which is likely to be very different to that seen in external beam radiotherapy. Watch this space.

Prof Dale Bailey Royal North Shore Hospital, Sydney (Modified text based on an original summary of ASCO 2015 supplied by Sirtex Medical. Image from RNSH, Sydney) Disclaimer: Dale Bailey holds an ARC Linkage Grant with Sirtex Medical as a partner and is designing a clinical trial to assess the dose-response relationship for SIRSpheres in mCRC at present (“QUEST”).

27

19

NET Update

Nuclear Medicine & Neuroendocrine Tumours – recent developments in NSW & beyond Dale Bailey PhD Royal North Shore Hospital, Sydney

MOST of us would be aware that the imaging and treatment of neuroendocrine tumours using nuclear medicine techniques has advanced rapidly in recent years. Neuroendocrine tumours (NETs) are relatively rare cancers which comprise a wide spectrum of tumours arising from neuroendocrine cells throughout the body with the gastrointestinal tumours being the most common. The NETs overexpress all subtypes of somatostatin receptors (sst) with the sst2 being the most widely overexpressed. As such, peptide-based Radionuclide Therapy (RNT) with yttrium-90 (90Y) and lutetium-177 (177Lu)-labelled somatostatin analogues are now a therapeutic option for patients who have failed to respond to conventional medical therapy. The original developments grew out of the Netherlands and a number of Australian centres were quick to follow their lead by offering the new scanning agents and therapeutic radionuclides. In particular, the Peter MacCallum Cancer Centre in Melbourne and Fremantle Hospital in WA were some of the earliest adopters of these new techniques. It is worth noting that these techniques remain still largely unavailable in the USA at present due to their local regulatory environment. The article contains news about a number of developments in this area.

FUNDING FOR LUTATE THERAPY IN NSW In NSW, treatment using [177Lu]-DOTA-Octreotate (“Lutate”) first became available at St George Hospital but other centres were unable to offer this therapy.

From 2015 funding for selected patients to receive Lutate therapy has been provided in a trial being run by the Cancer Institute NSW at St George Hospital and Royal North Shore (RNS) Hospital in Sydney with funding provided by the NSW Ministry of Health. To be eligible for treatment the patients need to have a proven neuroendocrine tumour which has progressed or is uncontrolled in spite of medical therapy. It is estimated that approximately 90 patients per year will be treated with the funding quantum that is being provided. Each patient receives four injections (“cycles”) of 8 GBq of Lutate at eight weekly intervals. Patients are mostly treated on an outpatient basis. An example of a patient who was treated at RNS is shown in figure 1. As part of the trial the centres involved are required to collect a range of data to examine the efficacy of the treatment. At RNS, usually 2-4 patients are treated on the same day and treatments take place one day per week.

ANSTO Another development is that ANSTO recently received 28 Gamma Gazette November 2015

Figure 1. DOTATATE (left) and FDG (right) PET scans in a 39 year old female treated at RNS show a dramatic response to Lutate therapy after only 2 cycles. One small focus remains visible in the right side of the skull (arrowed) on the DOTATATE scan. The scans were taken 4 months apart. (Images courtesy of Dr E.Bernard, RNS Hospital).

GMP certification for their 177Lu production facility.

This means that we now have a local source of 177Lu produced in the OPAL reactor at Lucas Heights, NSW. As we also have a local producer of the peptide required it means that Australia can be self-sufficient and not dependent on importing products for Lutate therapy.

The 177Lu (t.=6.7 days) is produced at ANSTO by an (n,g) reaction. Ytterbium-176 (176Yb) is irradiated to produce 177 Yb which decays with a half life of 1.9 hours to 177Lu. This method of production produces “no carrier added” (nca) 177Lu as the irradiated ytterbium target is readily separated chemically from the lutetium daughter product. An alternative method to make 177Lu using the 176Lu (n, g) 177Lu reaction will contain other isotopes of lutetium (176Lu, 177mLu) as contaminants in the final u

NET Update continued product. Due to the half life of nearly one week, 177Lu is readily transportable and ANSTO will be able to supply overseas facilities as well.

SYDNEY VITAL In NSW, the Cancer Institute has chosen to provide a large proportion of its funding through designated translational cancer research centres. These are intended to be large, collaborative, multi-disciplinary groups that break down traditional geographical boundaries in an effort to bring researchers and clinicians together.

Sydney Vital is the name of the translational cancer centre located on the northern campus of the University of Sydney’s medical school at Royal North Shore Hospital. It has three main programs of work, one of which is focused on improving the diagnosis and management of patients with neuroendocrine tumours. The project is led by A/Prof Nick Pavlakis, a Medical Oncologist, and myself. One of the things that the program provides is funding to employ a research fellow dedicated to the neuroendocrine tumour service. The current research fellow, Dr David Chan, is an advanced trainee in Medical Oncology but who is now spending a year full-time in the Department of Nuclear Medicine at RNS. This program has a number of projects associated with it focused on NETs including: • development of a comprehensive Figure 2. Study design for the Australian and New Zealand database of all NET patients including CONTROL NETS trial. demographics, histopathology, qualityof-life assessments, performance status, previous medical history and treatment, introduction of Lutate therapy and the long natural imaging, MDT (multidisciplinary team) meeting history associated with neuroendocrine tumours, discussions & outcomes, biochemistry, blood results very few randomised control trials of RNT have been and follow-up; completed and published to date. A number of the early • creation of a grading scheme for PET scans trials should be reported in the next 12-24 months. In (“NETPET” grade) that categorises the results Australia and New Zealand, we are about to commence from the DOTATATE and FDG imaging into a single a trial in neuroendocrine tumour patients that looks parameter; at the combination of Lutate with chemotherapy and • in collaboration with NICTA (National Information biological agents to better manage NET patients. & Communication Technology Australia) we are The trial is called CONTROL NETS (Capecitabine ON working on an an Internet-based tool to permit Temozolomide Radionuclide Therapy with Octreotate virtual MDT meetings. This is to allow remote Lutetium-177 in NeuroEndocrine Tumours Study). This participation in the net MDT meetings at RNS from trial is being run under the auspices of the Australasian across Sydney, NSW, Australia and beyond.

Gastro-Intestinal Trials Group (AGITG) by the NHMRC Clinical Trials Centre. Sponsorship for the initial phase It is fortunate that the funding for this program has of the trial is being provided by the Unicorn Foundation, become available at the same time as the rest of these the peak patient advocacy group in Australia and New exciting new developments for nuclear medicine in the Zealand representing NET patients, and ANSTO. The management of neuroendocrine tumours. design of the trial is shown in figure 2. The PIs for the trial are Prof Harvey Turner from Fiona Stanley Hospital, CONTROL NETS Perth (formerly at Fremantle Hospital) and A/Prof Nick For a number of reasons, such as the relatively recent Pavlakis from RNS Medical Oncology, Sydney. Two u 29

NET Update continued distinct groups will be studied: patients with primary pancreatic NETs (pNETs) and those with primary midgut NETs (mNETs). CONTROL NETS will be an important contribution to the management of NET patients and helps to reinforce Australia’s leading role in this field.

COMMNETS COMMNETS is an acronym for the Commonwealth Neuroendocrine Tumours group. This is a new association of clinicians and researchers from Australia, Canada, New Zealand and Singapore in the field of NETs. The use of radionuclide therapies, whilst originating in Europe, remains patchy there with availability and regulatory approval varying from country to country, while in the USA there is little in the way of 68Ga PET scanning and radionuclide NET therapy.

However, the COMMNETS countries all have similar access to the scanning and treatment modalities and largely share a common approach to their use. For this reason, the group is looking to develop large-scale trials

and research programs to overcome the fact that NETs are rare cancers and hence tend to take a long time to recruit subject to trials and for outcomes to become evident. The group are holding their inaugural meeting in Hawaii in November 2015 to undertake a research mapping exercise to identify suitable topics for future collaborative study.

Lutate therapy is now available to some degree in all mainland states of Australia and its role is becoming well established in the management of patients with neuroendocrine tumours. Australia has already made significant contributions in this field, in particular in the use of combined FDG and DOTATATE PET scanning and in the use of Lutate therapy. With the developments that are taking place as outlined in this short article this position will hopefully continue into the future of the benefit of patients with neuroendocrine tumours.

Dale Bailey PhD Royal North Shore Hospital, Sydney

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TEXT All text to be submittd in a word file format not PDF.

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30 Gamma Gazette November 2015

Lecturer / Senior Lecturer in Nuclear Medicine (Level A / B / C) • • •

School of Health Sciences, City East campus Adelaide, Australia Two (2) positions available

The University of South Australia is Australia’s University of Enterprise. Innovation and entrepreneurship are instilled in our students through industry informed teaching and learning. UniSA provides an exciting and dynamic environment for teaching and research that continually extends the boundaries of knowledge and its applications.

The School of Health Sciences has strong industry partnerships across public and private health, disability, ageing and education agencies and is equipped with outstanding laboratory and research facilities, including purpose-built anatomy facilities and a Virtual Environment Radiotherapy Training facility. The School is committed to high quality teaching and learning and research and has extensive industry collaborations and strong relationships with public and private health, disability, aging and education agencies.

The School currently has 2 opportunities available to teach into the Bachelor of Medical Radiation Science (Nuclear Medicine) program.

• 1 x Part-time (0.8 FTE), fixed term contract until 31 December 2016 (Teaching Academic Level A) • 1 x Full-time, 3 year fixed term contract (Teaching Academic Level A / B / C*) * Please note that appointment will be made in accordance with the skills, experience and qualifications of the successful candidate.

To be successful for appointment at Teaching Academic Level A you must hold a bachelor degree in Medical Radiation Sciences or equivalent, be eligible for National Registration with the Medical Radiation Practice Board of Australia and be eligible for licensing with the Environmental Protection Agency. Demonstrated expertise in the contemporary teaching and practice of nuclear medicine is also essential.

For successful appointment at Teaching Academic Level B or C, it is preferred that applicants possess either a doctoral qualification in a relevant field or a Masters in a relevant discipline together with professional/industry experience including eligibility for registration with the Medical Radiation Practice Board of Australia. In addition, applicants must have the ability to undertake teaching duties including the design and preparation of teaching activities and resources.

For further details including the position description, selection criteria and application lodgement details, please visit: www.unisa.edu.au/workingatunisa Applications close: 9.00am Friday 13 November 2015 ACDT Pursuant to the Children’s Protection Act 1993 (SA), this position has been deemed prescribed. It is a condition of appointment that the successful candidate provides the University with a Criminal History Assessment determining them fit to work with children. www.unisa.edu.au/workingatunisa The University is an Equal Opportunity Employer.

CRICOS PROVIDER NO 00121B

31

Case Study

Assessment of Mucosa-associated Lymphoid Tissue (MALT) lymphoma using [18F]-FDG PET/CT Heidi Fearnside, Elizabeth Bailey and Geoff Schembri Nuclear Medicine Department, Royal North Shore Hospital, Sydney

Background A 46-year-old female was admitted to the Emergency department in December 2014 with widespread oral and subcutaneous nodules, hypercalcaemia, increase in fatigue, weight loss, unsteadiness, blasts in her blood and progression of new subcutaneous nodules over her legs. She had a history of obesity, schizophrenia, Hepatitis C, chronic diarrhoea and recurrent bowel obstructions and MALT of the conjunctiva and bones diagnosed in 2010 with radiotherapy given to the left lateral 9th/10th ribs and left iliac crest, currently being treated with three monthly cycles of Rituximab.

Non contrast CT scans were performed (due to iodine anaphylaxis), manifesting interval increased number and size of innumerable subcutaneous nodules and increased subcutaneous stranding when compared to a previous CT from 2012, as seen in figure 1. There was no acute intra cranial pathology, nor intrathoracic or intra-abdominal nodal disease seen.

A PET/CT Scan was then performed in January 2015 to assess potential low grade to high grade transformation of MALT and the bulk of disease. The PET scan demonstrated small volume FDG avid lymphadenopathy in the bilateral facial cervical chains, supraclavicular fossae, right internal mammary nodes, bilateral perihilar, iliac, inguinal stations and innumerable intensely FDG avid cutaneous and subcutaneous nodules throughout the entire body with the largest deposits seen in the bilateral calf regions. No FDG avid osseous lesions were visualised (figure 2). The liver and

spleen were found to be within normal size and without abnormal focal uptake.

A biopsy was performed of the 7cm mass in the right medial thigh, showing diffuse large B-cell lymphoma, the morphology being more consistent with neoplastic follicles rather than colonised. The patient was treated with 3 cycles of R-CHOP and a repeat PET/CT study showed an excellent response to chemotherapy, with only one solitary site of persisting abnormal FDG uptake in the right thigh medially, which was reduced in size and avidity in comparison to the previous study (figure 3). This could represent a site of inflammation or persisting disease. The splenic enlargement and mild increase in uptake is most likely reactive to recent chemotherapy.

Discussion Mucosa-Associated Lymphoid Tissue (MALT) lymphoma is the most common extranodal small B cell Non-Hodgkin’s Lymphoma (NHL). The majority of NHL’s are of the diffuse large cell type and approximately 40% of NHL’s occur in extranodal locations.1 MALT is a clonal B-cell neoplasm and is the third most common type of NHL, approximately 7-8% of all B cell lymphomas.2 MALT lymphomas arise at sites that do not normally have lymphoid tissue, predominantly extranodal sites containing mucosae or glandular epithelia such as the gastrointestinal tract, salivary and lacrimal glands, lung, thyroid, conjunctiva, bladder and skin.3 It frequently recurs locally and has

Figure 1: CT scan showing multiple subcutaneous nodules, including (A) in the breast, (B) the thigh and buttock and (C) scattered throughout the pelvis.

32 Gamma Gazette November 2015

u

Assessment of Mucosa-associated Lymphoid Tissue (MALT) lymphoma using [18F]-FDG PET/CT

Figure 2: PET/CT Scan showing multiple cutaneous and subcutaneous nodules throughout the body, with the largest and most FDG avid lesions seen in the bilateral calf muscles (red arrow). the potential to systemically spread. MALT is generally regarded as indolent or low-grade lymphoma and therefore is not commonly assessed with PET imaging. However, high grade histological transformation can occur.

The indolent or low-grade nature of MALT pathophysiology does not adhere to the indications for PET/CT imaging or the usefulness of metabolic imaging.

However, in the instance of MALT high grade histological transformation PET/ CT imaging has proven to be an excellent tool for assessing extent of disease as well as treatment response.

References 1. Wotherspoon AC. Exotic MALT Lymphoma. GUT 2002; 51:148-150 2. Cohen SM, Petryk Varma M, et al. Non-Hodgkins Lymphoma of mucosa associated lymphoid tissue. Oncologist 2006; 11:1100-1117 3. The Non-Hodgkins Lymphoma Classification Project: A clinical evaluation of the International Lymphoma Study Group classification of Non-Hodgkins Lymphoma. Blood 1997; 89:3909-3918

Figure 3: A follow-up PET/CT scan after 3 cycles of R-CHOP shows a good response with one solitary site of persisting abnormal FDG uptake in the right thigh medially, which has reduced in size and avidity in comparison to the previous study.

33

Case Study

The value of delayed 18F-FDG PET/CT imaging in metastatic colorectal carcinoma James C. Player and Eva A. Wegner The Prince of Wales Hospital, Department of Nuclear Medicine and PET Abstract Colorectal carcinoma (CRC) is currently the third most prevalent form of malignancy in adults. The prognosis of this disease hinges greatly on the accurate detection and localisation of potential metastasis. The use of a dual time point protocol has been shown to improve the accuracy of PET/CT imaging in several cancer types.

This case study presents a 58-year-old male with recurrent CRC and bladder involvement. Highlighted is the value of delayed 18F-FDG PET/CT in identifying a bladder metastasis and confirming recurrent disease. In addition to the detection of nodal metastases, only on a 5 hour delayed PET/CT image of the pelvis was the bladder metastasis able to be visualised.

Introduction Colorectal carcinoma (CRC) is currently the third most prevalent form of malignancy in adults. As the second most common type of cancer in females and the third in males in 2012, colorectal carcinoma remains a significant contributor to global cancer mortality.1 Approximately one third of patients who are diagnosed with CRC succumb to the disease. Patient prognosis depends largely on location and detection of potential metastases, with CRC most commonly metastasising to regional lymph nodes, liver, lung, bone and brain.2 The addition of 18F-fluoro-D-deoxyglucose (FDG) positron emission tomography/ computerised tomography (PET/CT) has shown to greatly increase accuracy in the staging of CRC and impact patient management.3 However, some limitations exist in differentiating between physiological uptake and malignancy. In these cases, delayed PET/CT imaging may be implemented to further increase sensitivity and specificity.4 This case study describes the value of delayed 18F-FDG PET/CT imaging in the assessment of pelvic tumour recurrence and in particular, the detection of a bladder metastasis only visible on 5 hour delayed PET/ CT imaging in a patient with recurrent colorectal carcinoma.

Case Report Patient Presentation: A 58-year-old male experiencing four weeks of difficulty urinating in the context of previous metastatic colorectal cancer. A cystoscopy demonstrated a CRC metastasis within the posterior bladder wall. The patient presented to The Prince of Wales Hospital, Nuclear Medicine department for a PET/CT study to restage the recurrent CRC with known bladder involvement.

Past History: Initial diagnosis of metastatic rectal cancer approximately two years prior to presentation, treated with abdominoperineal resection of the primary tumour and subsequent chemo-radiotherapy.

This was followed nine months later by resection of a hepatic metastasis and further chemotherapy.

Scan Technique: A PET/CT study (Philips Ingenuity TF 128, Cleveland Ohio USA) was acquired from base of skull to mid-thigh at 55 minutes post-injection of 268MBq 18F-FDG. Further delayed PET/CT views of the pelvis were acquired at 4 hours and at 5 hours post-injection, following intensive oral hydration.

Scan Findings: No tumour recurrence at primary site and no liver metastases. Focal FDG uptake is present in multiple small nodal metastases in the porta hepatis, para-aortic and common iliac regions.

(Fig.1).

No abnormal FDG uptake identified in the pelvis. Due to intensely

34 Gamma Gazette November 2015

Figure 1: PET/CT images show focal uptake in para-aortic lymph nodes. avid radio-urine within the bladder, the known metastasis in the bladder wall could not be assessed on the initial one hour (standard) image.

Avid radiourine persisted within the bladder on the delayed four hour images despite hydration and voiding. On the 5 hour delayed images, following further hydration and voiding, the radiourine had completely cleared and focal intense FDG uptake was seen within the posterior bladder wall corresponding to the known metastasis within the bladder trigone (Fig. 2). A clear plane of separation between the bladder and the rectum indicates this is a discrete metastasis rather than direct posterior bladder wall invasion by tumour. No further bladder wall or pelvic lesions were detected.

A subsequent MRI of the pelvis confirmed the bladder wall metastasis. In addition, it demonstrated an area of mild enhancement and signal abnormality in the perineum and the presacral region. In view of the PET/CT findings of no abnormal uptake at these sites on the 1-hour and 5-hour images, this MRI finding was considered to be post-therapy change.

u

The value of delayed 18F-FDG PET/CT imaging in metastatic colorectal carcinoma

Discussion At present in most western countries approximately 50% of diagnosed patients can be treated with reasonable expectation of a cure, with 50% of those expected to survive for greater than five years.5 The patient in this case study did unfortunately exhibit recurrence of previously diagnosed colorectal carcinoma. The urinary symptoms experienced in the weeks leading to presentation led to the diagnosis of metastatic disease involving the bladder wall. This was confirmed through the use of delayed PET/CT imaging. It was not detected on the standard 1-hour imaging, as the presence of high concentrations of 18F-FDG in the urine masked the avid malignancy in the posterior wall of the bladder. The patient was instructed to consume large quantities of oral hydration and to void frequently in order to flush the radiourine from the bladder prior to acquisition. Markedly delayed imaging in this case proved essential to confirming the bladder involvement and proving it to be a solitary bladder metastasis rather than direct wall invasion.

It is also worth noting that dual time point imaging is useful in differentiating benign from malignant foci as the SUV will usually increase in malignant disease over the delay,6 and in this case the suspicious abnormalities in the presacral space and the perineum seen on the MRI were conclusively demonstrated to be post-therapy fibrosis rather than tumour recurrence. This was confirmed by no change in MRI appearances over the subsequent period of seven months.

The EANM guidelines for FDG PET and PET/CT suggest proper prehydration is usually sufficient to avoid misreading of PET/CT studies however notes that suspected bladder disease may warrant insertion of a transurethral catheter, administration of diuretic medication or delayed imaging.3 Of particular interest to this case is the extent of the delay required to visualise the bladder lesion. Whilst many PET/ CT departments routinely implement delayed imaging for suspected pelvic or abdominal disease, the chosen time point averages at approximately 2-3 hours post injection for reimaging.6 In this patient however, at 4 b) hours post-injection despite extensive hydration and voiding of the bladder prior to scanning, the presence of residual FDG in the urine continued to mask the site of disease in the bladder.

Only at the 5 hour time point was this lesion identifiable, therefore suggesting that in patients with suspected bladder disease a greater delay may be useful in accurately imaging the pathology. The delayed imaging should be undertaken at the earliest time point when radiourine is no longer seen in the bladder, which may take several hours.

Conclusion The standard 2-3 hour re-imaging delay proved insufficient to accurately identify the extent of this patient’s metastatic CRC on PET/CT, as the focal FDG avid lesion in the bladder continued to be masked by radioactive urine. Only on 5 hour delayed images was this site able to be visualised and accurately reported, confirming and characterising the metastatic lesion. In addition, other sites of abnormal signal which appeared suspicious on the MRI were correctly characterised as posttherapy changes in view of the lack of metabolic activity on the initial 1-hour and delayed 5-hour PET/CT. This case therefore encourages extensively delayed imaging after intensive hydration and voiding in cases where bladder involvement is suspected. The interval before repeat imaging is acquired should be sufficient for the physiological FDG uptake in the bladder to completely clear, which was 5 hours for our patient.

References 1. Yang, S, et al. (2015). Signet-ring cell carcinoma of the colon: A case report of a 9-year-old boy. Oncology Letters, 10(1), 1632-1634.

Retrieved 22 September, 2015, from http://dx.doi.org/10.3892/ ol.2015.3403 2. El-Halabi, M, et al. (2014). Colon cancer metastasis to mediastinal lymph nodes without liver or lung involvement: A case report.

Oncology Letters, 8(1), 2221-2224. Retrieved 22 September, 2015, from http://dx.doi.org/10.3892/ol.2014.2426 3. Culverwell, A. D, Chowdhury, F. U & Scarsbrook, A. F. (2012).

Optimizing the role of FDG PET-CT for potentially operable metastatic colorectal cancer. Abdominal Imaging, 37(1), 1021-1031. Retrieved 23 September, 2015, from http://dx.doi.org/10.1007/s00261012-9855-9 4. Boellaard, R, et al. (2010). FDG PET and PET/CT: EANM procedure guidelines for tumour PET imaging: version 10. European Journal of Nuclear Medicine Molecular Imaging, 37(1), 181-200. Retrieved c)22 September, 2015, from http://dx.doi.org/10.1007/s00259009-1297-4 5. Hartley, J, et al. (2000). Patterns of recurrence and survival after laparoscopic and conventional resections for colorectal carcinoma.

Annals of Surgery, 232(2), 181-186. Retrieved 22 September, 2015, from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1421127/ 6. Lan, X-L, et al. (2008). The value of dual time point 18F-FDG PET imaging for the differentiation between malignant and benign lesions. Clinical Radiology, 63(1), 756-764. Retrieved 22 September, 2015, from http://dx.doi.org/10.1016/j.crad.2008.01.003

Figure 2: Axial PET/CT slices of the bladder at 55mins (Left), 4 Hours (Middle) and 5.5 Hours (Right). FDG avid lesion in posterior bladder wall clearly visible on 5.5 Hour image.

35

Peer Reviewd Paper

Lutetium-177 DOTATATE Production with an Automated Radio-pharmaceutical Synthesis System Alireza Aslani1,2*, Graeme M Snowdon1, Dale L Bailey1,3, Geoffrey P Schembri1,2, Elizabeth A Bailey1, Nick Pavlakis2,4, Paul J Roach1,2 1. Department of Nuclear Medicine, Royal North Shore Hospital, Sydney, Australia 2. Sydney Medical School, University of Sydney, Sydney, Australia 3. Faculty of Health Sciences, University of Sydney, Sydney, Australia 4. Department of Medical Oncology, Royal North Shore Hospital, Sydney, Australia

Abstract Objective(s): Peptide Receptor Radionuclide Therapy (PRRT) with yttrium-90 (90Y) and lutetium-177 (177Lu)-labelled SST analogues are now therapy option for patients who have failed to respond to conventional medical therapy. In-house production with automated PRRT synthesis systems have clear advantages over manual methods resulting in increasing use in hospital-based radiopharmacies. We report on our one year experience with an automated radiopharmaceutical synthesis system.

Methods: All syntheses were carried out using the Eckert & ZieglerEurotope’s Modular-Lab Pharm Tracer® automated synthesis system. All materials and methods used were followed as instructed by the manufacturer of the system (Eckert & Ziegler Eurotope, Berlin, Germany).

Sterile, GMP-certified, no-carrier added (NCA) 177Lu was used with GMP- certified peptide. An audit trail was also produced and saved by the system. The quality of the final product was assessed after each synthesis by ITLC- SG and HPLC methods.

Results: A total of 17 [177Lu]-DOTATATE syntheses were performed between August 2013 and December 2014. The amount of radioactive [177Lu]- DOTATATE produced by each synthesis varied between 10-40 GBq and was dependant on the number of patients being treated on a given day. Thirteen individuals received a total of 37 individual treatment administrations in this period. There were no issues and failures with the system or the synthesis cassettes. The average radiochemical purity as determined by ITLC was above 99% (99.8 ± 0.05%) and the average radiochemical purity as determined by HPLC technique was above 97% (97.3 ± 1.5%) for this period.

Conclusions: The automated synthesis of [177Lu]-DOTATATE using Eckert & Ziegler Eurotope’s Modular-Lab Pharm Tracer® system is a robust, convenient and high yield approach to the radiolabelling of DOTATATE peptide benefiting from the use of NCA 177Lu and almost negligible radiation exposure of the operators.

Keywords: Automated synthesis Lutetium-DOTATATE, Neuroendocrine tumours, Peptide Receptor Radionuclide Therapy

*Corresponding author Alireza Aslani, Department of Nuclear Medicine, Royal North Shore Hospital, St Leonards, Sydney, Australia.

Tel: +61 2 99264440; Fax: +61 2 99264099; E-mail: alireza.aslani@health.nsw.gov.au © 2015 mums.ac.ir All rights reserved This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons. org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Please cite this paper as: Aslani A, Snowdon GM, Bailey DL, Schembri GP, Bailey EA, Pavlakis N, Roach PJ. Lutetium-177 DOTATATE Production with an Automated Radiopharmaceutical Synthesis System. Asia Oceania J Nucl Med Biol. 2015; 3(2): 107-115.

36 Gamma Gazette November 2015

Introduction Neuroendocrine tumours (NETs) comprise a wide spectrum of tumours arising from neural crest cells throughout the body.

While once considered rare, recent epidemiologic data has shown increasing incidence with little change in mortality, suggesting that there has been significant under-diagnosis in the past (1). These tumours are often slow growing and may go undiagnosed for long periods of time leading to patients presenting with advanced disease. Symptoms are frequently vague leading to delays in diagnosis. The appropriate management of these tumours is best handled through a multidisciplinary approach as their diagnosis and treatment crosses a range of specialities.

Neuroendocrine gastrointestinal tumours are the most common.

Terminology has been varied over the years and these are often broken down into carcinoid (mid-gut) tumours and endocrine pancreatic neoplasms. While these two groups have different behaviour, they are often encompassed in the single term - gastroenteropancreatic neuroendocrine tumours (GEP-NETs). Many of these tumours (the so called carcinoid tumours) produce endocrine syndromes due to the overproduction of a range of hormones. The fact that NETs overexpress subtypes of somatostatin (SST) receptors (2) allows for diagnosis and treatment with SST analogues. While all five SST

Lutetium-177 DOTATATE Production with an Automated Radio-pharmaceutical Synthesis System

receptor subtypes are overexpressed to some degree (3), SST2 is the most widely overexpressed. Peptide Receptor Radionuclide Therapy (PRRT) has gained substantial interest in the last few years (4). Radiolabelled somatostatin analogues are now considered for patients who have failed to respond to conventional medical therapy (5,6). The two most commonly used radioisotopes are yttrium-90 (90Y) and lutetium-177 (177Lu). These radioisotopes differ in terms of their emitted radiations, particle energy, physical half-life and tissue penetration(7,8). The radiopharmaceuticals being used for this therapy are DOTATATE, DOTATOC and DOTANOC, all of which are labelled via the DOTA chelator to either 90Y or 177Lu (7). These radiopharmaceuticals have a range of SST affinities though all have good affinity for SST2. Although the synthesis and purification of these radiopharmaceuticals can successfully be carried out manually in the laboratory, the use of automated synthesis systems is gradually increasing (9). These automated systems have clear advantages over manual methods which have resulted in their increasing installation and use in hospital-based radiopharmacies. At our institution we use no-carrier added (NCA) 177Lu labelled with a locally synthesised peptide for the PRRT of patients with well-differentiated NETs. The [177Lu]-DOTATATE (referred to as “NCA-LuTATE”) is synthesised inhouse using an automated synthesis system. Here we report on our one year, 17 syntheses experience with this formulation.

Methods There are a number of reports in the literature using and detailing various automated radiochemistry systems used for synthesising radio-pharmaceuticals (RP) labelled with gallium-68 68Ga), 177Lu and other radioisotopes (10-12). However, the number of reports in the literature using automated synthesis systems for [177Lu]-DOTATATE is scarce except for de Decker and Turner (13) who recently reported their experience of automated synthesis systems for [177Lu]-DOTATATE synthesis. Automated RP synthesis systems use generic synthesis procedures with minor modifications tailored to the specific needs of the institution and can also include chemical analysis and detection systems such as High Pressure Liquid Chromatography (HPLC) units. As a result, over time, these setups evolve and are modified to improve productivity and can become unique to the institution. The system reported here was the Eckert & Ziegler Eurotope’s ModularLab Pharm Tracer® automated synthesis system.

All materials and methods used were followed as initially instructed or later modified by the manufacturer of the system (Eckert & Ziegler Eurotope, Berlin, Germany - subsequently referred to as the vendor or manufacturer) from whom the automated RP synthesis system and synthesis cassettes were obtained.

Reagents As recommended by the manufacturer, all reagents were high purity pharmaceutical grade, unless stated otherwise. The exact grade as well as the source of the reagents used was also their recommendation.

Water puriss p.a (FLUKA Trace SELECT® 95305) used in the preparation of the majority of reagents was obtained from Sigma-Aldrich, Australia. Sodium chloride 0.9% for injection in 50 mL glass bottles (INJ089) were obtained from Phebra (Lane Cove, NSW, Australia). The L-ascorbic acid puriss p.a (FLUKA 33034-100 G), sodium hydroxide monohydrate (Trace SELECT® 01968- 25 GF; ≥99.9995% pure), and 200 proof ethanol (HPLC / spectrophotometric grade, 459828-1L) were also obtained from Sigma-Aldrich, Australia.

177 Lu was produced by a different method to that commonly reported previously. Two distinct methods for reactor production of177Lu can be used: the more commonly used approach is to directly irradiate high purity 176Lu via the reaction 176Lu(n,γ) 177Lu, while the alternative is to irradiate 176Yb as in 176Yb(n,γ) 177Yb which decays with a 1.9 hour half-life to 177Lu. The latter method has the advantages that (a) there is no carrier lutetium present, and so is referred to as “no-carrier added” lutetium (NCA [177Lu]) , and (b) there is no 177mLu produced, which has a physical half-life of 160 days and therefore presents a significant radioactive waste storage and disposal problem. A further advantage of the NCA [177Lu] is that it requires less peptide to label the necessary active amount of [177Lu]-DOTATATE for the therapy. This is the production methodology for the 177Lu utilised at our institution.

The DOTATATE, or DOTA-(Tyr3) – octreotate (where DOTA = 1,4,7,10 – tetraazacyclododecane – 1,4,7, 10-tetraacetic acid) was obtained from Auspep (Melbourne, Australia). The peptide is provided as a 1 mg powder which is subsequently dissolved in 1 mL of water and used in 200 µL aliquots. The DOTATATE peptide is certified as Good Manufacturing Practice (GMP) grade.

The preparation of the required [177Lu]-DOTATATE reagents and chemicals are shown in Table 1. This table is used as a quick instruction guide for the preparation of chemicals at our centre.

The 177Lu (NCA 177LuCl3) was obtained from ITG (Isotope Technologies Garching GmbH, Germany) through a partnership with the Australian Nuclear Science and Technology Organisation (ANSTO), Sydney, Australia. The amount of radioactive 177Lu ordered for each synthesis was based on the number of patients to be treated per synthesis and an estimate of 80% synthesis yield. The prescribed dose to be injected was a notional 8 GBq per patient (14).

Synthesis Cassettes and Automation The synthesis of [177Lu]-DOTATATE can be separated into three parts.

These are: a) the modules, arranged according to the specific RP being synthesised; b) the synthesis cassettes on which the appropriate chemicals, reagents, filters, columns, etc are attached; and c) the computer system that executes the software which, in turn, operates the valves and syringes on the cassettes producing the required RP. Since the system is computer-controlled, an audit trail is always maintained which is a requirement for GMP production certification.

There is a specific synthesis cassette for the production of [177Lu]DOTATATE. The same system is also currently being used for the production of other PET RP, such as [68Ga]-DOTATATE and [68Ga]PSMA (Prostate-Specific Membrane Antigen) using separate synthesis cassettes as well as another for a simple elution of the 68Ge/68Ga generator. All production cassettes are obtained from the vendor. These cassettes are sterile and for single-use only.

As with the cassettes, there is a specific computer template program for each RP synthesis process. These templates are also provided by the vendor. These are subdivided into programs for the cassette pressure testing, terminal sterilisation filter testing, running the HPLC analysis and, in the case of [168Ga]-DOTATATE and [168Ga]PSMA, also for eluting the 168Ge/168Ga generator. The software also allows programming and modifications to the templates via a graphical user interface (GUI).

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Lutetium-177 DOTATATE Production with an Automated Radio-pharmaceutical Synthesis System

Lutetium-177 (177Lu) Lutetium-177 (t½ = 6.7 days) emits both β- and γ radiation during its decay to stable 177Hf. The principal β- emission has an average energy of 0.149 MeV with 78.6% abundance. There are a number of small abundance γ photons emitted, with those of interest for imaging using the gamma camera being 0.208 MeV (11% abundance) and 0.113 MeV (6% abundance). The fact that few γ photons are emitted allows many 177Lu therapies to be performed on an outpatient basis from a radiation safety perspective in many jurisdictions despite the patient being administered up to 8-10 GBq of 177Lu, with exposure from contact with treated patients being comparable to that seen with a 99mTc bone scan. The 177Lu we have used for all syntheses was sterile, GMP-certified, no-carrier added 177Lu in the form of lutetium chloride (177LuCl3) and is supplied in a volume of 0.5 mL (0.04 M HCl solution). The radioisotope generally arrives at our centre one day prior to the actual day of synthesis. The radioactivity was calibrated for the day and time the synthesis was due to be carried out. The radioactivity ordered was requested to be approximately 10 GBq per patient which allowed for an approximate 80% product yield providing a final 8 GBq dose per patient. To date, up to four patient doses have been produced in a single synthesis, i.e., an approximate amount of 40 GBq of NCA 177Lu at start of synthesis.

Automated Radiolabelling Process Once the sterile synthesis cassette is removed from its packaging and all connections tightened, it is attached to the Modular Lab’s synthesis cassette module. The radiolabelling process is performed in three steps. The first step tests the cassette for any leaks. This step, also known as the Cassette Pressure Test, applies a pressure of 200 kPa to various sections of the cassette. This is software controlled. This test is performed by attaching the cassette to a high purity nitrogen gas supply with its pressure regulator adjusted to deliver 200 kPa of pressure. A visual progress graph is also displayed (Figure 1). If there is no loss of pressure to below 100 kPa, the test is considered to have passed and the cassette is suitable for use.

However, if the test fails, the cassette is removed from the module, all connections re-tightened and test repeated. If the test fails again, the cassette is rejected and sent back to the manufacturer and replaced. The process of pressure testing the cassette takes approximately five minutes. On completion, the cassette pressure test process log is saved on the computer for audit trail purposes. On passing the test, the necessary pre-prepared reagents are placed in the appropriate containers of the synthesis cassette and 177Lu vial connected. The empty containers, the waste bottle and product vial are then attached. The product vial and waste bottle are placed

Table 1: Checklist of chemicals used for [177Lu]-DOTATATE synthesis.

38 Gamma Gazette November 2015

Lutetium-177 DOTATATE Production with an Automated Radio-pharmaceutical Synthesis System

Figure 1. Pressure test trace indicating a pressure test Pass (top) and a Fail (bottom).

Figure 3. Average [177Lu]-DOTATATE yields and radiochemical (RC) purity by ITLC and HPLC.

in a specially designed Perspex container boxes to reduce any βradiation dose to the operator. The vial containing the 177Lu is kept in its original lead shielded container also to reduce radiation dose to the operator. The second step of the synthesis phase is similarly driven by the Modular Lab Pharm Tracer® software. The duration of this process is approximately 45 minutes and is the main step of the entire process. The movement of all liquids is driven by a 10 mL syringe attached to the syringe-driver module. This phase involves a number of different steps, including washing of various sections with 0.9% saline. Briefly, the Waters tC18 Light reverse phase silica cartridge (also known as C18 ion exchange or SepPak® cartridge) is initially primed (wetted) with ethanol followed by 0.9% saline.

The [177Lu]-LuCl3 is then transferred from its vial (radioactivity vial) into the reactor which contains the DOTATATE peptide. To ensure

that the entire radioactivity has been removed from the delivery vial, it is then washed with the buffer solution and the remaining radioactivity is transferred to the reaction vial. Once all the lutetium is in the reaction vial together with the peptide, the mixture is heated at 80ºC for 20 min. The cassette is then rinsed twice with 0.9% saline to remove any residual radioactivity from the fluid paths. The crude product from the reaction vial is then removed and kept in the syringe for five minutes to cool. Once cooled, it is then passed through the C18 cartridge to remove any unbound [177Lu]-LuCl3.

Both the C18 cartridge as well as the reaction vial are then rinsed with 0.9% saline to recover any residual product. The product, now trapped in the C18 cartridge, is eluted by first passing an ethanol/ water mixture (47.5%:52.5% ratio) and then 0.9% saline into the final product vial. To ensure sterility, the final product is passed

Figure 2. Example of representative images from a single individual showing [68Ga]DOTATATE PET scan (MIP image) (left) and after infusion of ~6.4 GBq of [177Lu]-DOTATATE at four time points. The gamma camera images are geometric mean (GM) images that have been corrected for attenuation using a preacquired transmission scan and converted to units of radioactivity (kBq).

The distribution of disease on [177Lu]-DOTATATE images is identical to that seen on the preceding diagnostic [68Ga]DOTATATE scan.

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Lutetium-177 DOTATATE Production with an Automated Radio-pharmaceutical Synthesis System

through a 0.22 µm filter. The total volume of the final product is 18 mL. The software provides a graphical display of each step and progress of the synthesis. On completion, the synthesis process is digitally saved on the computer for audit purposes.

The third phase of the synthesis involves testing of the integrity of the 0.22 µm filter. This is known as the Filter Pressure Test and is, again, driven by the Modular Lab Pharm Tracer® software. The only operator intervention required is the removal of the 0.22 µm filter and needle from the product vial and putting it into the waste bottle prior to the test. The test is performed by subjecting the filter to 200 kPa of pressure. If pressure is maintained above 100 kPa, the test is considered to have been successful and the product is sterile for patient use. However, if the pressure falls below 100 kPa, the test is considered to have been unsuccessful and there is a chance of the product being unsterile. To rectify this, the product needs to be drawn-up manually in a 20 mL syringe and passed through a new 0.22 µm filter into another sterile vial. To date, this has not occurred at our centre. On completion, the filter pressure test process log is saved on the computer for audit purposes. The trace produced by the software is similar to the ones produced for the Cassette Pressure Test. After removing a 0.2 mL sample from the product for quality control purposes, the product is ready to be administered to the patient.

Analysis and Quality Control The quality control of the resulting product is done by two methods - Instant Thin Layer Chromatography (ITLC) as well as High Pressure Liquid Chromatography (HPLC). These are performed using the 0.2 mL sample taken directly from the final [177Lu]-DOTATATE product.

Instant Thin Layer Chromatography (ITLC) The ITLC test is used to determine the percentage of [177Lu]-DOTATATE and 177Lu impurities in the final product. The ITLC paper strips are counted in a laboratory gamma-counter (PerkinElmer Wizard2® Automated Gamma Counter, PerkinElmer Downers Grove, IL, USA) and results entered into a spreadsheet (Microsoft Excel Version

Figure 4. A typical chromatogram report for radiolabelled [177Lu]DOTATATE product.

40 Gamma Gazette November 2015

2010) for final calculation and analysis.

For the determination of percentage [177Lu]-DOTATATE and 177Lu impurities, 0.1 mol/L citrate buffer (pH= 5) with ITLC-SG paper (Pall Corporation, East Hills, New York); Rf (free 177Lu) = 0.8–1.0, Rf (177Lu peptide) = 0.0–0.3 is used.

High Pressure Liquid Chromatography (HPLC) The HPLC analyser was provided by the vendor and was driven by the Modular Lab Pharm Tracer® software. The HPLC unit comprises a Knauer Smartline D14163 pump (Knaur, Berlin, Germany) with Knauer Online Degasser V7620 (Knauer, Berlin, Germany), ACE3 C18 column 150×3 mm (Advanced Chromatography Technology, Aberdeen, UK), flow rate 0.6 mL.min-1, water/acetonitrile (ACN)/ 0.1% trifluoroacetic acid with 22% ACN. A 0.04 mL sample is used to determine the percentage [177Lu]-DOTATATE content of the final product.

Results A total of seventeen [177Lu]-DOTATATE syntheses were performed between August 2013 and December 2014 in our laboratory. All syntheses were carried out using the methods described above and were performed in the Department of Nuclear Medicine, Royal North Shore Hospital within a hot-cell (Model: NMCGa-68; TEMA SINERGIE, Italy) located in a purpose-built radiopharmaceutical laboratory. The amount of radioactive [177Lu]-DOTATATE produced by each synthesis varied between 10 - 40 GBq and was dependant on the number of patients being treated on a given day.

Patients During this period a total of 13 individuals (9 males and 4 females) were treated with [177Lu]-DOTATATE on an eight week cycle, equating to a total of 37 individual treatment administrations. All patients were treated on an out-patient basis. Median age at start of treatment for males and females were 60.4 years (range from 32.7 to 70.5 years) and 61.9 years (range from 50.4 to 74.8 years), respectively. The median body surface area (BSA) at start of treatment for males and females were 1.87 m2 (range from 1.59 to 2.16 m2) and 1.75 m2 (range from 1.49 to 1.88 m2), respectively.

Five patients received the full course of 4 therapy cycles during this period. The remaining 8 patients received fewer than 4 cycles either due to being partway through their course of 4 treatments or treatment being suspended due to poor health. An example of the initial biodistribution of the [177Lu]-DOTATATE and subsequent retention and biodistribution at a number of time points up to four days post-injection is shown in Figure 2 along with the patient’s corresponding [68Ga]-DOTATATE scan. The whole body retention of the radiolabelled peptide averaged over all patients treated to date exhibits a generally bi-exponential pattern with clearance rates of 2.1±0.6 h for the fast and 58.1±7.2 h for the slow components respectively. Approximately 25% of the original amount of administered [177Lu]-DOTATATE (approximately 2 GBq) is remaining in the patient when they leave the department approximately four hours after commencing treatment.

The patients were scanned on a SPECT/CT dual head gamma camera (Siemens Symbia T6, Hoffman Estates, IL, USA) using a medium energy collimator (208 keV ±10% PHA window) at 30 min (planar only) and then again at 4, 24, and 96 h (planar and SPECT).

The SPECT images were 120 projections at 15 sec per projection at 4 h and 20 sec per projection at 24 and 96 h.

Lutetium-177 DOTATATE Production with an Automated Radio-pharmaceutical Synthesis System

[177Lu]-DOTATATE Syntheses Although there were no issues and failures with the synthesis cassettes, some minor modifications were made to the volumes of the chemicals, buffers, etc. under the remote guidance of the manufacturer to improve the quality and product yield. These modifications were made as a part of ongoing improvements and quality control in response to user comments and feedback.

Radiochemical Quality Control The radiochemical purity of the final product was measured using ITLC as well as HPLC. The use of HPLC for [177Lu]-DOTATATE syntheses was initiated recently to have an additional measure of the quality of the final product as well as to compare and experiment on alternative manufacturers’ [177Lu]-LuCl3. The results demonstrated that the average radiochemical purity as determined by ITLC was above 99% (n=17; 99.8 ± 0.05%) and the average radiochemical purity as determined by HPLC technique was above 97% (n=3; 97.3 ± 1.5%) for this period (Figure 3). A typical chromatogram of the radiolabelled product is shown in Figure 4.

Cassette and System Failures As our centre had extensive previous experience with the automated synthesis system for the radiolabelling of [68Ga]-DOTATATE (15), the majority of the initial teething problems had already been addressed and rectified. As a result, there have not been any failures during any of the [177Lu]-DOTATATE syntheses.

Record Keeping and Audit Trail Good record keeping and an audit trail is mandatory for GMP system compliance. For this purpose, electronic copies (in PDF format) of the pressure tests, syntheses, and HPLC tests were automatically saved by the automated synthesis system. In addition, patients’ details, quality control results (ITLC and HPLC), system failures, and synthesis and pressure test batch numbers were recorded in a laboratory log book. This was predominantly for fast access to previous work. A summary of the above was also recorded on a spread sheet (Microsoft Excel Version 2010) and electronically saved on the synthesis PC as well as a hardcopy printed and stored at the Department of Nuclear Medicine.

Discussion There has been an increase in the development of targeted radionuclide therapies, especially for cancer. The main benefit observed so far with peptide targeted therapies labelled with β-emitting radionuclides is to stabilise and delay further tumour growth rather inducing significant tumour shrinkage (response).

However treatment can improve pain control as well as reduce hormone related symptoms, leading to improved quality of life.

Prior to the wide availability of the automated synthesis systems, the synthesis and preparation of [90Y]-DOTATATE or [177Lu]-DOTATATE was carried out using “bench-top” manual methods (9). Although there are still centres that use manual methods, there is a move towards the use of automated synthesis systems. Benefits of the automated system include reduced radiation exposure to the operators. Using the manual method and assuming that 400 doses of 7.4 GBq are prepared by four workers, the average equivalent dose to the worker has been reported (16) to be 23 ± 11 mSv and 14 ± 6 mSv for finger top and ring dose, respectively. With the automated synthesis system the finger doses and other exposure is negligible.

In terms of their final product, both synthesis methods are similar, but not identical. One difference between the two is the amount of starting materials and chemicals that are used. These include the peptide and buffers. The [177Lu]-LuCl3 used in the automated synthesis at our centre is NCA 177Lu. In contrast, the manual synthesis method reported in the literature (17) utilises 177Lu that contains chemical carriers. The implications of these added carriers are that larger amounts of DOTATATE peptide (up to 600 µg) are required during the synthesis to ensure that the required amounts of radiolabelled [177Lu]-DOTATATE is produced in the final product compared with approximately 200 µg using the NCA 177Lu. These extra amounts of the required peptide can contribute to the overall cost of the procedure.

The carrier-added 177Lu also has the disadvantage of containing additional impurities. During the production of the carried-added 177Lu by the 176Lu(n, γ)177Lu reaction via thermal neutron bombardment of enriched lutetium oxide some 177mLu is also produced. 177mLu has a long half-life (160.4 days) that will require the synthesis cassettes and other waste products, including potentially urine, to be stored for months to years prior to disposal (16).

As compared to the manual method, the automated synthesis system has two disadvantages: initial setup and ongoing consumable (cassettes only) costs. However this cost, in our opinion, is acceptable compared with the benefits that the automated system provides.

Conclusions The automated synthesis of [177Lu]-DOTATATE using Eckert & Ziegler Eurotope’s Modular-Lab Pharm Tracer® system is a robust, convenient and high yield approach to the radiolabelling of DOTATATE with large amounts of radioactive 177Lu, with almost negligible radiation exposure of the operators. The method we use also benefits from the use of no-carrier added 177Lu by reducing impurities, waste products and the mass of peptide required for adequate labelling.

Much lower radiation doses to the operator is another significant advantage of the automated method. In our one year experience the system has performed reliably delivering the required dose for [177Lu]-DOTATATE therapy of patients with somatostatin-expressing neuroendocrine tumours.

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Lutetium-177 DOTATATE Production with an Automated Radio-pharmaceutical Synthesis System

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Article history Received: 17 Feb 2015 Revised: 27 Apr 2015 Accepted: 30 Apr 2015 Article Info Article type: Technical note

Reprinted with permission of the authors and the Asia Oceania Journal of Nuclear Medicine & Biology (aojnmb.mums.ac.ir). ANZSNM members are encouraged to consider submitting original research, case studies, clinical, preclinical, radiopharmaceutical science and medical physics articles to this peer-reviewed free open access journal covering all aspect of nuclear medicine. The aim of the AOJNMB is to provide a forum for the exchange of clinical and scientific information of scientists and physicians working in the field of nuclear medicine & biology and associated professions.

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Australian and New Zealand Society of Nuclear Medicine