Molecular Radiotherapy Dosimetry by BIR Publishing

4 JUNE 2014

MOLECULAR RADIOTHERAPY DOSIMETRY

Venue: Oxford University CPD: 6 CREDITS

BIR Annual Congress 2014: 22-23 October, London

Welcome and thank you for coming to the â&#x20AC;&#x2DC;Molecular radiotherapy dosimetryâ&#x20AC;&#x2122; event organised by the BIR in association with the IDUG. This booklet contains the abstracts and biographies for each speaker. This meeting has been awarded 6 RCR category I CPD credits. CPD certificates will be distributed by email within two weeks of the meeting once the online delegate survey has been completed. Please complete the online delegate survey using the below link. We will use your valuable feedback to improve future conferences. https://www.surveymonkey.com/s/molecularradiotherapy We hope you find the day interesting and enjoyable.

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Programme 9:00 Registration and refreshments 9:30 Welcome and introduction to IDUG Miss Claire Hooker, Principal Physicist, East Kent Hospitals University NHS Foundation Trust 9:40 Comparison of molecular radiotherapy and radiotherapy Professor Katherine Vallis, Group Leader, CRUK/MRC Oxford Institute for Radiation Oncology Session 1 - I-131 Chair : Claire Hooker, Principal Physicist, East Kent Hospitals University NHS Foundation Trust 10:00 Clinician’s view Dr Laura Moss, Consultant Clinical Oncologist, Velindre Cancer Centre, Cardiff 10:30 Scientist’s view Dr Jonathan Gear, Clinical Scientist, Joint Department of Physics, The Royal Marsden Hospital 11:00 Refreshments and poster presentations Session 2 – Neuroendocrine Chair: Shaunak Navalkissoor, Consultant Nuclear Medicine Physician, Royal Free Hospital 11:30 Clinician’s view Dr Prakash Manoharan, Consultant Radiologist and Nuclear Medicine Physician, The Christie NHS Foundation Trust 12:00 Scientist’s view Dr Lefteris Livieratos, Medical Physicist in Nuclear Medicine, Guy’s and St Thomas’ Hospitals 12:30 Lunch and poster presentations Session 3 – SIRT and proffered work Chair: Dr Prakash Manoharan, Consultant Radiologist and Nuclear Medicine Physician, The Christie NHS Foundation Trust 13:30

Clinician’s view Dr Ricky Sharma, Group Leader, CRUK-MRC Oxford Institute for Radiation Oncology, University of Oxford Honorary Consultant in Clinical Oncology, the Oxford University Hospitals NHS Trust

14:00 Scientist’s view Mr Michael Tapner, Research and Development Project Manager, Sirtex 14:30

Proffered talk 1: 3D Volumetric dosimetry using dose point kernel convolution for Y-90 SIRT Ms Catherine Scott, Trainee Clinical Scientist, King’s College Hospital NHS Foundation Trust

14:45

Proffered talk 2: Establishing a reliable methodology for molecular radiotherapy dosimetric assessment of Lu-177- DOTATATE in a paediatric population Dr Matt Aldridge, University College London Hospital

15:00 Poster prizes 15:05 Refreshments and poster presentations Session 4 – Future Chair: Dr Glenn Flux, Clinical Scientist, Royal Marsden Hospital 15:30 New MRT agents: challenges for chemistry, radiobiology and dosimetry Professor Phil Blower, Professor of Imaging Chemistry, Division of Imaging Sciences and Biomedical Engineering, King’s College London 16:00 Monte Carlo in MRT Dr Emiliano Spezi, Department of Medical Physics, Velindre Cancer Centre, Cardiff 16:30 MRT clinical trials Dr Matt Guy, Consultant Physicist, Clinical Lead for Medical Physics, Head of Imaging and NM Physics, University Hospital Southampton 17:00 Close of meeting

Please remember to complete the online delegate survey using the below link: https://www.surveymonkey.com/s/molecularradiotherapy Your certificate of attendance will be emailed to you within the next two weeks once these have been completed.

BIR Annual Congress 2014: 22-23 October, London

Speaker profiles

Dr Matt Aldridge University College London Hospital Matthew is based at the Institute of Nuclear Medicine, University College London Hospital. He has a keen interest in Molecular Radiotherapy research, with relevant publications in the use of 131I-mIBG and 177Lu in the adult and paediatric population. He is part of a team currently evaluating 177Lu-DOTATATE in neuroblastoma as part of a formal Phase 2 trial. Professor Phil Blower Professor of Imaging Chemistry, Division of Imaging Sciences and Biomedical Engineering, King’s College London After a BA in Natural Sciences (Cambridge) and DPhil in Chemistry (Sussex), Phil Blower gained postdoctoral experience in inorganic chemistry at Indiana University and Oxford University. His first academic post was a joint appointment at Kent and Canterbury Hospital (Radiopharmacy) and the University of Kent (Radiochemistry), where he combined the two roles to develop a number of new radiopharmaceuticals for imaging and therapy, including the earliest Re-186 and Re-188 targeted therapeutic radiopharmaceuticals and pioneering use of copper radionuclides for PET in Europe. In 2006 he moved to King’s College London to take up a Chair in Imaging Chemistry in the Division of Imaging Sciences and Biomedical Engineering, where, as Head of the Imaging Chemistry and Biology Dept., he has built a large interdisciplinary research group with wide interests covering radiopharmaceutical chemistry and biology for PET, SPECT and radionuclide therapy, including a continuing focus on copper radionuclides (especially in hypoxia imaging) as well as technetium, rhenium, gallium and fluorine. He is PI or co-PI on current grants worth about £25m, including a Cancer Research UK/EPSRC Cancer Imaging Centre and a Wellcome/EPSRC Medical Engineering Centre. He has published more than 130 peer-reviewed papers and supervised 19 successful PhD students. He has served on various peer review panels for international grant awarding bodies and journals and is Editor in Chief of Nuclear Medicine Communications. Dr Jonathan Gear Clinical Scientist, Joint Department of Physics, The Royal Marsden Hospital Dr Jonathan Gear began his career at the Royal Marsden NHS Foundation Trust in 2002 working on a number of molecular radiotherapy dosimetry projects including SPECT based 3D tumour dose calculations following I-131 mIBG therapy for neuroblastoma and I-131 NaI dosimetry for metastatic thyroid carcinoma. In 2004 Jonathan began a PhD at the Institute of Cancer Research under the supervision of Dr Glenn Flux. In the course of his PhD Dr Gear pioneered the use of polymer gel dosimetry for molecular radiotherapy, demonstrating methodology that could be used to independently verify the

accuracy of internal dosimetry procedures and provide a basis for standardisation. Methodologies developed from this work have been incorporated into his current role as a clinical scientist and he continues to be involved in a number of dosimetry projects which have resulted in numerous publications and presentations at both national and international meetings.

Dr Matt Guy Consultant Physicist, Clinical Lead for Medical Physics, Head of Imaging and NM Physics, University Hospital Southampton Dr Matt Guy is Clinical Lead for Medical Physics and Head of Imaging Physics at University Hospital Southampton. He has extensive experience across both diagnostic and therapeutic applications of Nuclear Medicine, including PET/ CT, and in the development of CT imaging techniques. Whilst working at the Institute of Cancer Research, he co-developed one of the first patient-specific dose planning systems for Molecular Radiotherapy and also worked extensively on improving the quantification of high count-rate SPECT imaging. He has developed a range of novel diagnostic and therapy processing tools, including a combined gamma camera and CT simulation toolkit to help develop and validate new diagnostic and therapy procedures. Other research interests include understanding and correcting respiratory motion during imaging, the application of adaptive image filtering and automated shape analysis in neurological imaging. He has been involved in both IPEM and BIR working parties on Nuclear Medicine and currently co-chairs the Internal Dosimetry User Group (IDUG), whose aim is to deliver practical help to clinical and scientific staff undertaking Molecular Radiotherapy. Miss Claire Hooker Principal Physicist, East Kent Hospitals University NHS Foundation Trust Clair is Co-Chair of the Internal Dosimetry User Group. She is Head of Nuclear Medicine Physics at East Kent Hospitals University NHS Foundation Trust and acts as MPE in Nuclear Medicine for Kent and Canterbury Hospital and William Harvey Hospital. Claire studied Physics at Nottingham University graduating in 2004. Following this she gained an MSc in Radiation Physics at University College London and completed the Grade A training scheme at the Royal Berkshire Hospital, Reading. Claire developed a special interest in radionuclide dosimetry while working as a Clinical Scientist at King’s College Hospital from 2009-2014.

Dr Lefteris Liveratos Medical Physicist in Nuclear Medicine, Guy’s and St Thomas’ Hospitals Dr Livieratos is a Medical Physicist in Nuclear Medicine at Guy’s & St Thomas’ Hospitals and NIHR Senior Clinical Lecturer in Imaging Sciences at King’s College, London. He has worked in PET methodology at Hammersmith Hospital alongside the MRC PET Oncology and PET Cardiology research groups on radiotracer image-based quantification and novel schemes for patient motion correction such as respiratory motion correction of PET projection data. He

subsequently worked as a clinical scientist at Guy’s & St Thomas’ involved with diagnostic and therapeutic applications, including the clinical implementation of the first SPECT/CT in Europe with diagnostic 16-slice CT. He is involved with teaching of radionuclide imaging physics at King’s College and the supervision of students and trainee clinical scientists. His research interests include multimodality imaging, image quantification and tracer kinetics methodology for translational applications and patient-specific dosimetry in targeted radionuclide therapy. Dr Prakash Manoharan Consultant Radiologist and Nuclear Medicine Physician, The Christie NHS Foundation Trust Dually accredited in Radiology and Nuclear Medicine, with sub specialised fellowships in nuclear medicine (UK), oncology body MRI/CT (UK) and nuclear medicine/PET CT/ advanced radionuclide therapy (UMICH,Ann Arbor,USA). Clinical lead for the MRI, PET CT and Diagnostic Nuclear medicine programmes at The Christie. Key achievements Development and delivery of NET molecular imaging and targeted therapy. Introduction and development of MRI services, especially in relation to liver imaging and leading the development of WB MRI service locally. Part of the team that developed the NET MDT and successfully applied for recognition by the European NET society as a European Centre of Excellence. Involved in clinical trials and research related to molecular/functional imaging and radionuclide targeted therapy. Key architect in developing an integrated imaging strategy for molecular and functional imaging which has been incorporated into the The Christie 20:20 vision. Dr Laura Moss Consultant Clinical Oncologist, Velindre Cancer Centre, Cardiff Dr Laura Moss is a consultant clinical oncologist specialising in the treatment of patients with thyroid cancer. She qualified from the University of Wales, College of Medicine in 1993 and undertook her Specialist Registrar training in oncology on the South Wales training scheme. She became a consultant at Velindre Cancer Centre in 2002. She founded Thyroid Cancer Forum-UK in 2005 which currently has ~240 consultant members. She is the current NCRI Thyroid Cancer Subgroup Chair, an EORTC Endocrine Cancer Task Force member and Honorary President of Thyroid Cancer Support Group Wales. She has a particular interest in anaplastic thyroid cancer and launched the National Anaplastic Thyroid Cancer Tissue Bank and Database (NATT) project in 2013.

Ms Catherine Scott Trainee Clinical Scientist, King’s College Hospital NHS Foundation Trust Following the completion of her physics degree at the University of Surrey almost 3 years ago Catherine has been training as a medical physicist at King’s College Hospital. She has chosen to specialise in imaging with ionising radiation, dividing her time between nuclear medicine and radiation protection. The work presented here was undertaken as part of her MSc project. Dr Ricky Sharma Group Leader, CRUK-MRC Oxford Institute for Radiation Oncology, University of Oxford Ricky Sharma is a Group Leader at the CRUK-MRC Oxford Institute for Radiation Oncology, University of Oxford and an Honorary Consultant in Clinical Oncology at the Oxford University Hospitals NHS Trust. Dr Sharma is also Chair of the Cancer Teaching Committee in the Oncology Department at the University of Oxford, the Programme Leader for one of the major imaging themes (radiotherapy) within the Cancer Research UK-EPSRC Oxford Cancer Imaging Centre and Co-Chair of the Liver Cancer Multidisciplinary Team (MDT) meeting at the Oxford University Hospitals NHS Trust. The Oxford University Hospitals Liver MDT offers a wide range of treatment options to patients with primary liver cancer and cancer that has spread to the liver from other organs, including surgery, ablation of different types, SIRT, stereotactic ablative body radiotherapy and trials of novel drug therapies. At a national level, Dr Sharma Co-Chairs the Early Phase Trials Workstream of the United Kingdom NCRI Clinical and Translational Radiotherapy (CTRad) Group and he leads a national clinical trial sponsored by the University of Oxford, called FOXFIRE, which has recruited over 300 patients with metastatic colorectal cancer across the UK and is now open to recruitment across 3 continents as “FOXFIRE-Global”. This clinical trial is an example of partnership between the University of Oxford, the NHS, the National Cancer Research Institute, Cancer Research UK and Sirtex Medical Ltd. Overall survival results from over 1000 patients in this collaboration will be reported by Dr Sharma and colleagues in 2017. Dr Emiliano Spezi Department of Medical Physics, Velindre Cancer Centre, Cardiff Emiliano Spezi works as HCPC registered research clinical scientist in Velindre Cancer (Cardiff) where he leads R&D for Medical Physics. He gained his degree in Physics from the University of Bologna (Italy) and his PhD from Cardiff University discussing a thesis on Monte Carlo simulation of Intensity Modulated Radiotherapy. Emiliano is member of several professional organisations including: the Institute of Physics, the Institute of Physics and Engineering in Medicine, the European Association of Nuclear Medicine, the European Society for Therapeutic Radiology and Oncology, the Clinical and Translational Radiotherapy Research Working Group, and he chairs the Database and IT

solutions subgroup of the NCRI Radiotherapy Trials QA Group. Emilianoâ&#x20AC;&#x2122;s research interests include: Image Guided Radiotherapy, Radionuclide Imaging, High Performance Computing and Radiotherapy Planning and Dosimetry for Molecular Radiotherapy. Since 2012 he actively participates to MetroMRT (Metrology for Molecular Radiation Therapy) a joint research project within the European Metrology Research Programme lead by the National Physical Laboratory (Teddington). Mr Michael Tapner Research and Development Project Manager, Sirtex Michael completed a Bachelor of Applied Science at UTS in Sydney and then worked in Academia for 15 years. During this time he worked in the area of drug metabolism and liver disease. In 2004 he joined Sirtex in the Clinical department, where he was involved in the setting up of the FOXFIRE and SIRFLOX studies. In recent years he has transferred to R&D and is now involved in projects focused on dosimetry and the challenges of Y90. Professor Kate Vallis Group Leader, CRUK/MRC Oxford Institute for Radiation Oncology Kate studied medicine at St Bartholomewâ&#x20AC;&#x2122;s Hospital, and trained in Clinical Oncology at the Hammersmith Hospital. After obtaining her PhD at the University of Edinburgh she was appointed as Staff Radiation Oncologist at the Princess Margaret Hospital, Toronto, specialising in breast cancer, and as Scientist at the Ontario Cancer Institute. In 2006 Professor Vallis took up her current positions as Group Leader at the CR-UK/MRC Gray Oxford Institute for Radiation Oncology and Consultant Clinical Oncologist at the Oxford University Hospitals NHS Trust. Her research focuses on molecular imaging and targeted radiotherapy.

Abstracts (where supplied) Welcome and introduction to IDUG Miss Claire Hooker IDUG provides a forum for clinical and scientific staff to discuss dosimetry for molecular radiotherapy (MRT) and to offer practical help to members. Membership of the group is open to all physicists, technicians, radiographers, radiologists, oncologists and other professionals with an active involvement and interest in expanding the role of dosimetry in molecular radiotherapy. The group holds regular (usually quarterly) meetings to discuss matters of relevance to MRT. The meetings have an activity theme and a named lead for projects. The aim of the projects is to produce a series of practical guides for MRT dosimetry. I-131: Clinicianâ&#x20AC;&#x2122;s view Dr Laura Moss Until recently there was little consensus on the management of differentiated thyroid cancer. Now with the development of national thyroid cancer guidelines and a network of interested thyroid cancer clinicians across the UK we have the ability to develop and run multicentre randomised studies and have the potential to standardise and optimise patient management. We have made progress with regards to whom to treat with radioiodine remnant ablation and what activity of radioiodine to administer but we have a long way to go especially in the setting of metastatic disease. A proportion of patients with differentiated thyroid cancer will develop radioiodine refractory disease, why this occurs is unknown. Despite the investigation of multiple therapeutic manoeuvres to reverse the refractoriness there has been limited success and this remains a significant clinical challenge. All UK centres use fixed activities of radioiodine for thyroid remnant ablation and the vast majority of patients requiring radioiodine therapy for recurrent and metastatic disease receive fixed and arbitrary activities. Dosimetry based methods of prescribing do not currently feature in routine clinical practice and there are many unanswered questions. Are we currently doing our patients a disservice by using fixed activities? Would the introduction of dosimetry improve patient care and outcomes? The presentation aim is to outline the current situation and to highlight the areas of interest and concern for clinicians and patients.

I-131: Scientist’s view Dr Jonathan Gear Since its first use in 1946, I-131 for molecular radiotherapy has grown from strength to strength used in the form of NaI for benign and malignant thyroid disease, mIBG for neuroendocrine therapy, Lipiodol for HCC and numerous labelled antibodies for non-Hodgkins lymphoma. However, despite its wide use and a large number of publications relating to iodine dosimetry, quantitative iodine imaging remains challenging and to date there have been very few published dose-response relationships for these therapies. We review the literature, highlighting the key publications from the last 70 years. The different approaches to dosimetry will be discussed concentrating on issues pertinent to iodine imaging. Recent recommendations for quantitative I-131 imaging will be reviewed and examples given of clinical and hypothetical scenarios employing dosimetry. Methodologies will be critically appraised including the use of I-123 & I-124 for guiding and predicting therapy administrations. Educational aims: Gain an understanding of the inherent issues in quantitative I-131 imaging and the different approaches employed. Reflect on the validity of I-131 dosimetry techniques and the necessity and practicalities of such imaging regimens. Neuroendocrine: Clinicians view Dr Prakash Manoharan MRT in NET has been accepted as a ‘standard’ therapy. The talk will briefly discuss the evolution of the current ‘standard therapies’, the challenges the clinical team face when discussing MRT with patients, the difficulties in accepting/ modulating ‘standard’ doses for these therapies and the need to reduce side effects ideally with accurate dosimetry. The final part of the talk will be a series of questions to the community to open up a discussion forum. Neuroendocrine: Scientist’s view Dr Lefteris Livieratos Targeted radionuclide therapy with radio-labelled peptides such as [177LuDOTA]octreotate, has shown in recent years promising results for the treatment of neuroendocrine tumours. Dosimetric data may have a role in the process of better understanding therapy outcome as well as in further optimisation of delivery of therapy on a personalised basis. However, the feasibility of dosimetry is dependent on various, often practical, aspects such as access to patient imaging and resources such as software and protocols. Furthermore, as radio-peptide targeted therapy becomes more widely available, the ability to collate larger scale dosimetric data from multiple centres may be feasible in order to inform potential correlations between dose and therapeutic outcome with large patient numbers. However, in order

to achieve dosimetric comparisons across multiple centres and/or compatible methodologies, it is necessary to obtain an estimate of the variance due to differences in imaging protocols, analysis techniques and software. In this overview, we examine some of the aspects that may affect dosimetry with the aim to set the scene of technical background that may underpin clinical application in radio-peptide targeted therapy. SIRT: Clinicianâ&#x20AC;&#x2122;s view Dr Ricky Sharma Learning points: 1. NICE Guidance for metastatic colorectal cancer, primary intrahepatic cholangiocarcinoma and hepatocellular carcinoma (HCC) states that current evidence on the safety of selective internal radiation therapy (SIRT) is adequate. 2. NHS England has commissioned SIRT in 10 centres via the Commissioning through Evaluation programme; patients with intrahepatic cholangiocarcinoma or metastatic colorectal cancer (refractory to 2 lines of chemotherapy, or intolerant of chemotherapy) should be referred to the commissioned centres for Liver MDT discussion. 3. There are 2 types of dosimetry for SIRT: Partition model (glass microspheres) versus body surface area dosing (resin microspheres). The volume of liver to be treated is common to both models. The Normal Tissue Complication Probability Model states that sufficient normal liver tissue must be spared to avoid liver failure. References: NICE interventional procedure guidance documents 401, 459, 460: guidance.nice.org.uk/ Kennedy A, Nag S, Salem R, Murthy R, McEwan AJ, Nutting C, Benson III A, Espat J, Bilbao JI, Sharma RA, Thomas JP, Coldwell D. Recommendations for Radioembolization of Hepatic Malignancies Using Yttrium-90 (Y90) Microsphere Brachytherapy: A Consensus Panel Report from The Radioembolization Brachytherapy Oncology Consortium (REBOC). INT J RAD ONCOL BIOL PHYS 2007, 68: 13-23 Nicolay NH, Berry DP, Sharma RA. Liver metastases from colorectal cancer: role of radio-embolization with systemic therapy. NATURE REV CLIN ONCOL 2009, 6: (12): 687-97.

SIRT: Scientistâ&#x20AC;&#x2122;s view Dr Michael Tapner The science behind SIRT has changed little since the first human patients were treated in the 1990â&#x20AC;&#x2122;s. Activity administration formulae have historically been based on safety data derived from study populations, with modifications being made over the last two decades on the basis of treatment population safety. These formulae, and their appropriate modifications, will be outlined. Technological developments in imaging hardware and software have provided the potential to determine patient dosimetry on an individual patient basis. Developments in this field have been focused on two areas. The first is the potential of Tc99 MAA remaining within the liver, following injection to determine the lung shunt fraction, to provide a prognostic tool for personalised dosimetry. The second, more recent approach, has focused on the potential of Y90 PET to determine delivered dose at the time of therapy. Refinement of these two approaches has the potential to deliver substantial improvements in both safety and efficacy, with the former allowing for effective treatment planning and the latter providing the potential to determine the response to therapy on the day of implantation. The final challenge to optimising dosimetry is an understanding of how to determine the activity of Y90 to be administered and the challenges therein. Developments in the field of Y90 activity assessment will be outlined. 3D volumetric dosimetry using dose point kernel convolution for Y90 SIRT Ms Catherine Scott Aim: Selective Internal Radiotherapy (SIRT) is used to treat inoperable liver tumours via the administration of microspheres containing Y90. The purpose of this work was to create a programme which can produce a personalised, quantitative map of absorbed dose, to facilitate the estimation of dose to tumour and non-tumour liver tissue. Methods: The programme, written in Matlab (Release 2011b, MathWorks, Inc., Natick, Massachusetts, United States), reads in registered SPECT-CT DICOM datasets acquired during pre-treatment imaging using Tc99m-MAA as a proxy for the biodistribution of the Y90-microspheres. In an automated process the image counts are normalised to the administered activity of Y90. A 3D dose point kernel is then constructed using data from ICRU report 72, with voxels of the same dimensions as the SPECT dataset. The two are convolved to convert the activity into absorbed dose rate. Finally, the dose is corrected for the residence time of the Y90, which as the microspheres are permanently implanted, is dependent only on the physical half-life of Y90. The dose information is then displayed as a contour map superimposed on the CT data, simultaneously yielding anatomical and absorbed dose information. Regions of interest, such as tumours, can be outlined on the CT and dose volume histograms will be produced for these regions.

Conclusions: A software program has been written which can convert patient SPECT-CT images into personalised, 3D dose maps in a fast and automated fashion. The resulting dose maps can be displayed and analysed by the user to gain quantitative dosimetric information. Establishing a reliable and reproducible methodology for molecular radiotherapy dosimetric assessment of 177Lu-DOTATATE in a paediatric population Dr Matt Aldridge Treatment of neuroendocrine tumours with peptide receptor radionuclide therapy (PRRT), principally targeting the somatostatin receptor subtype 2 (sstr-2) is an established and safe technique in adult patients. Expression of sstr-2 by neuroblastoma in children makes treatment with 177Lu-DOTATATE worthy of investigation. A phase 2 trial is in progress to evaluate the efficacy and safety of this treatment in neuroblastoma. It incorporates patient-specific whole body, tumour and normal organ dosimetry. Avoidance of unacceptable bone marrow and renal toxicities is essential for safety, and knowledge of tumour dose is desirable for correlation with response. Children with relapsed or refractory high-risk neuroblastoma are assessed for suitability for in-patient PRRT with 177Lu-DOTATATE by 68Ga-DOTATATE PET/CT. The administered activity of the first fraction of 177Lu DOTATATE is weight-based (75MBq/Kg). Activity for subsequent administrations at 8 to 12 week intervals depends on the whole-body radiation dose received and the haematological toxicity from previous administrations. Whole-body dose is determined by ceiling-mounted scintillation probe monitoring, performed regularly by carers over 4 days; and planar imaging, performed using a GE D670 gamma-camera at 6 time points with additional SPECT/CT for critical organ and tumour dose distribution/dosimetry. We present here, a methodology for molecular radiotherapy dosimetry as utilised in this formal phase 2 clinical trial, in which accurate whole-body, tumour and organ-sensitive doses are a key component for improving the therapeutic index and minimisation of toxicity. This methodology involves accurate determination of time-activity curves derived from multiple sampling of counting methods, planar and SPECT/CT imaging. In addition, commercial software designed to accurately define and quantify volumes and radiopharmaceutical uptake for Radio-Isotope therapy treatment planning purposes, is being validated. It is anticipated that the data from this trial will help inform other 177LuDOTATATE studies in adults and other potential somatostatin positive paediatric tumours.

New MRT agents: challenges for chemistry radiobiology and dosimetry Professor Phil Blower Radionuclide therapy has been part of the daily routine of nuclear medicine since the birth of the specialty more than half a century ago, beginning with the use of P-32 in he 1930s. Beta emitting radionuclides have been the main tools in this endeavour, but recent successful clinical trials with the alphaemitter Ra-223 have reawakened interest in clinical use of alpha emitters. In addition, Auger electron emitters could be added to the clinicianâ&#x20AC;&#x2122;s arsenal of radionuclides. However, clinical developments need to be accompanied by both a greatly improved understanding of the relevant radiobiology, including clearer relationships between dosimetry, microdosimetry and the biological effects of radiation at the cellular level, and improved chemistry to deliver the new radionuclides, not simply to tumours but to the right parts of tumours, the right cells and the right parts of the cell. This presentation will address the limitations in the state-of-the-art, focusing on recent developments in radiochemistry including chemical and to simplify radiolabelling and improve target to background ratios and effectively deliver new and short half-life radionuclides, and the interplay between these and radiobiological challenges (e.g. the role of hypoxia, sub-cellular localization, microdosimetry) that need to be addressed to be able exploit fully the potential of targeted radionuclide therapy. Monte Carlo in MRT Dr Emililano Spezi Following the European legislation on medical exposure to ionizing radiations (Council directive 97/43 EURATOM 1997), individualized dosimetry is mandatory. However, in molecular radiotherapy (MRT) treatments details including dose prescription, number of cycles, fractionation scheme and administered activity per course are based on clinical evidence and not on full patient specific dose assessment. Contrary to standard clinical practice in external beam radiotherapy, in MRT dose calculation to target and organs at risk (OAR) is still performed, in the best case scenario, using deterministic algorithms on prebuilt anthropomorphic phantoms and tabulated data. The need for more patient-specific methods for dose calculations and treatment planning in MRT has been acknowledged. Monte Carlo (MC) calculation algorithms are regarded as the most accurate methods for radiation transport in both reference and clinically relevant conditions. The use of 3D MC-based systems as a reference dosimetry tool and/or as a treatment planning system is an area of considerable interest and of great potential development. The use of 3D MC-based systems will allow scientists to take into consideration the actual mass, density and geometry of targets and OARs, decreasing the uncertainty of the delivered dose and improving the quality of treatments. This presentation reports on progress in the development of Raydose a MC code for image based dosimetry in MRT.

MRT clinical trials Dr Matt Guy Molecular Radiotherapy (MRT) has formed part of Nuclear Medicine for more than six decades. Yet, compared to external beam radiotherapy, its use and dissemination has been relatively minor. This has led to fragmentation, with relatively small patient populations spread across sites, with individual centres often choosing to follow different administration routines. Without standardisation, the MRT community is often left without options for evidence-based optimisation. In the absence of optimisation, some treatments remain stranded in the investigational phase of development, which can have a significant impact on their incorporation into patient pathways and for the availability of funding. Despite these shortcomings, MRT continues to grow and as it becomes more widespread, scope for utilising cutting edge clinical imaging, metrology and dosimetry techniques increases, challenging the range of current practice. The move from reliance solely on traditional beta emitters to alpha and Auger emitting radionuclides represents both a challenge and opportunity for MRT standardisation. Together with the growing availability of patient genetic profiling, dosimetry and radiology models are likely to be pushed to or beyond their limitations. In such an environment, will standardised, randomised trials emerge for MRT and provide the Level 1 evidence MRT may need to truly flourish?

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