WCI Newsletter 2020 9 Vital role of research reactors in isotope production

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01.Lead Article

1. Global Trends in the Use of Medical Radioisotopes and the Vital Role of Research Reactors in Their Production1

Meera Venkatesh2,

2020 September

Former Director,

Vol.9 – Issue 9

Division of Physical and Chemical Science, IAEA

01 Lead Article

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02 Isotope-related News

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03 Sketches from the Secretariat

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04 Future Conferences and Events

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Jong Kyung Kim President Nigel Stevenson Immediate Past President Paul Dickman President-Elect

Abstract: Radioisotopes have been used in healthcare since almost eight decades, evolving continuously with advancements in bio-medical sciences as well as computation and imaging technologies. While the initial use of medical isotopes was primarily for therapeutic purposes (Cobalt-60 in teletherapy and Iridium-192 in brachytherapy; and Iodine-131 and Phosphorus-32 in in-vivo nuclear medicine), the last few decades of the last century

Bernard Ponsard Chair, Industrial Applications Keon Wook Kang Chair, Medical Applications Timothy Payne Chair, Environmental Applications Carlo R. ChemalyChair, Info.Exchange& Cooperation Syed M. Qaim Chair, Education and Training Meera Venkatesh Chair, Publication Paul Dickman Chair, ICI Coordination Ira N. Goldman Chair, Long-Term Funding Woo-Geun Song Secretary-General

1) Presented by MEERA VENKATESH, et al, at the International Conference on Research Reactors, 25-29 November 2019, Held in Buenos Aires, Argentina. Reproduced with permission from IAEA. The conference proceedings will be published shortly by the IAEA and available on the iaea.org/publications. 2) Also, Former Head, Radiopharmaceuticals Division Bhabha Atomic Research Centre and Senior General Manager, Board of Radiation and Isotope Technology, Department of Atomic Energy, India

WCI Secretariat 18F Seoul Forest IT Valley 77 Seongsuil-ro, Seongdong-gu, Seoul, Korea ON ISOTOPES WORLD COUNCIL TEL: +82-2-3490-7141 Email: Secretary@wci-ici.org www.wci-ici.org

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witnessed a steep growth in diagnostic nuclear medicine with the advent of the most widely used medical radioisotope, Technetium-99m and its versatile nature, earning it the name 'Work horse of nuclear medicine'. The new millennium witnessed a paradigm shift with the phenomenal growth in the production and use of positron(β+) emitting isotopes, especially Fluorine-18 to provide high resolution images. Thanks to the innovations in the various related fields, nuclear medicine has a niche, unique place in medical diagnosis as well as treatment of several ailments, especially cancers. Therapeutic applications using particulate (especially β- emitting radionuclides) has witnessed a resurgence and growth in the past 2 to 3 decades, and a large number of radioisotopes have yielded excellent results, among which Lutetium-177, Samarium-153, Rhenium-188/186 and Yttrium-90 deserve special mention. In the recent years, the use of alpha emitters for therapy has gained much attention owing to the very impressive results in certain types of cancers. 'Theranostics', the use in both diagnosis and therapy, has evolved as the new approach for personalized therapy, owing to the availability of suitable radioisotopes. From the beginning, Research reactors have played a vital role in the production of radioisotopes, which is often not known to the end user. As most of the research reactors that supplied the isotopes to the world aged, long shut downs were unavoidable, leading to short supply of isotopes, bringing forth the importance of having the fleet of research reactors around the world in operation to cater to the global needs. Although radioisotope production in accelerators has seen a huge growth, it is beyond doubts that research reactors are essential for production of a huge range of important radioisotopes in large quantities and at affordable cost. Preamble: Radioisotopes have been put to numerous applications owing to the unique properties of radiations such as easy traceability, ability to destroy cells and causing changes on matter. Although nuclear power applications are widely known, the non-power applications which cover a wide range of areas, are often not well known. The surveys conducted in the past have shown that the economic benefits from non-power applications of radioisotopes and radiation are huge and far outweigh those from nuclear power (J.Nucl.Sci.Tech. 39(2002)1020-1124). Among the various areas of applications of radioisotopes, medical applications are among the earliest of applications and the most widely known. With the installation of research

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reactors since the 1950s, their applications for peaceful uses were pursued avidly. Several radioisotopes were produced and supplied, especially for healthcare applications. Phosphorus-32, Iodine-131 have been used in therapy since nearly eight decades and are continued to be used. Production of radioisotopes in particle accelerators and nuclear reactors witnessed steady fast growth with establishment of research reactors and cyclotrons all over the world; and their use in healthcare fields also grew in several areas. This article will focus on the important role of research reactors in production of radionuclides for healthcare, especially in management of fatal diseases such as cancer, cardiac ailments, neurological disorders etc. Introduction: Medical applications of radioisotopes could be categorized based on their use such as for therapy or diagnosis or for obtaining special materials for use in healthcare. A further classification is based on the mode of administration of the radioisotope. The following are the common terminologies in this context. Nuclear Medicine is the specialty in which a radiolabeled substance known as radiopharmaceutical is administered into the patient, either for diagnostic or for therapeutic purpose. Sealed radioactive sources are used for treatment of diseases either by external shining of the radiation on the lesion, known as Teletherapy or by placing the source in contact with the lesion, known as Brachytherapy. Sealed radioactive sources are used for sterilization and ‗Radiation Medical Sterilization‘ is used worldwide widely to sterilize most of the disposables such as syringes, needles, gauze etc. as well as prosthetics. Apart from the above widely practiced applications, sealed radiation sources are used to prepare novel high-performance materials, although such use is niche and infrequent. Understandably, the physical properties of the radionuclides should be amenable for the intended use. For use in diagnostic procedures, the radiation will need to be traceable while therapy of cancers or sterilization of medical equipment, will need strong radiation that can destroy living cells. Over the past several decades, a wide range of radionuclides have been explored for a vast spectrum of uses. Radioimmunoassay (RIA), a Nobel Prize winning technology (1977), for measuring minute quantities of hormones and biomolecules in human samples like serum with very high

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sensitivity and specificity, revolutionized the practice of endocrinology and oncology as these values helped in accurate diagnosis and follow-up of therapy. A radionuclide is used as tracer in these assays and a related procedure known as Immunoradiometric assays (IRMA) and Iodine-125 is the most used radionuclide in these ‗in-vitro‘ tests. RIA grew rapidly in the following decades and ‗RIA kits‘ that could be used in pathology labs for measuring large number of important hormones and cancer antigens were developed. While RIA/IRMA kits are still used for measurement of some hormones, most of these assays have shifted to the use of other tracers such as enzymes or fluorescent markers. Hence this is not detailed further here. However, it is notable that I-125 is predominantly produced in nuclear reactors and has niche unique uses as tracer in in-vitro assays as well as in brachytherapy.

Overview of the radionuclides used and Global Trends: Radiopharmaceuticals/Nuclear Medicine: For diagnostic nuclear medicine, radionuclides that emit photons which can be imaged with high sensitivity and with a short half-life (generally few hours to a few days), amenable chemistry and devoid of particulate emission are suitable. Gamma rays in the range of 100-200 keV energy are suitable for imaging using a gamma camera (which generally employ NaI(Tl) crystals for detection). Annihilation photons (511 keV) from positron emitters when measured (using appropriate detectors) in a coincidence mode provide images with high resolution and hence positron emitters with suitable features are useful in diagnostic nuclear medicine. The advances in detector and computation technologies have enabled 3-dimensional imaging with high sensitivity (Single Photon Emission Computed Tomography or SPECT and Positron Emission Tomography or PET). For internal therapy, radiation with high ‗Linear Energy Transfer‘ (LET) are effective. So, radionuclides that emit particulate radiations such as -,  or electrons, with half-life of a few days and amenable chemistry are suitable for therapeutic nuclear medicine; the adjacent figure illustrating the range of different particles in tissues gives an idea about the importance of choosing the appropriate radionuclide based on the target tissue size.

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In addition, presence of imaginable photons is advantageous for following the path of the injected radiopharmaceuticals and dose calculations. However, for external use as a source of radiation (to either treat cancers or for medical sterilization or prepare novel materials for use in healthcare), the radionuclide should have a long half-life (years) and emit high energy gamma radiations. While the range of radionuclides used in nuclear medicine – both for diagnosis and therapy – is very wide, the choice is limited for use as a radiation source. Nuclear medicine has steadily grown over the past decades. Diagnostic nuclear medicine is predominantly used in oncology, cardiology, neurology and functional imaging of many of the human systems. Currently nearly all vital organs can be imaged for anatomical as well as functional parameters. It is noteworthy that the WHO survey in 2012 showed that ~31% of the deaths were due to cardiovascular diseases and there is an annual increase of ~19 Million cancer patients in the world. Diagnostic nuclear medicine provides invaluable information to the doctors for making accurate diagnosis, plan treatment and monitor patients for treatment efficacy. Therapy in nuclear medicine is most often used for treating cancers and a few other conditions such as hyperthyroidism. Though therapy aims at delivering radiation dose to the target organ/lesions, it is important to ensure that the radiation dose is accurately delivered to the desired tissues. Hence monitoring therapy through imaging is commonly followed. In the recent years, there has been focus on ‗personalized therapy‘ wherein the treatment is planned and followed using a diagnostic imaging using the same biomolecule labelled with a suitable radionuclide of the same element or a surrogate nuclide. This combination of diagnostic and therapeutic procedures for planning personalized treatment is known as ‗Thera(g)nostics‘ and a matched pair of nuclides (which could either be of the same element or a surrogate element) are used. As mentioned earlier, use of radionuclides in medicine has a long history. With the establishment of research reactors, several radioisotopes were produced and supplied to the hospitals. The most used were P-32, I-131, Au-198, Cr-51, Na-24 and Hg-19; and among these, I-131 continues to be an important therapeutic radioisotope, and P-32 is still used in few countries for therapy. The rest are currently seldom used in radiopharmaceuticals. In the recent years, Gold isotope Au-198 is explored as a therapy nuclide. The advent of Tc-99m, with excellent physical characteristics ideally suited for imaging and its availability from a Mo-99/Tc-99m radionuclide generators, resulted in a paradigm shift. With the availability of Tc-99m generators in the market, during the 1970‘s, a wide range of Tc-99m tagged radiopharmaceuticals were developed for anatomical as well as functional imaging of the important organs. Tc-99m soon earned the name of ‗Work-horse‘ of diagnostic nuclear

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medicine. Tc-99m continues to be the most used diagnostic radionuclide as more than 80% all diagnostic scans employ Tc-99m based radiopharmaceuticals, amounting to about 40 Million studies annually. Tc-99m is availed from Mo-99-Tc-99m Generators and the Mo-99 is produced using Research Reactors, most often through (U, fission) reaction or neutron capture on Mo-98. The entry of positron (β+) emitter Fluorine-18 for PET imaging resulted in a paradigm shift in the nuclear medicine practice; and the most widely used PET radiopharmaceutical, F-18 labelled fluorodeoxyglucose (F-18-FDG) was named the molecule of the millennium! Diagnostic PET imaging with a range of PET isotopes produced in particle accelerators continues to be widely used in cancer management. The commonly used and significantly explored radionuclides in nuclear medicine are listed below. Diagnostic Radionuclides: SPECT: 99mTc; 67Ga; 111In; 123I; 201Tl PET: 18F; 68Ga; 11C; 82Rb; 13N; 124I; 15O; 64Cu; 89Zr Gamma Imaging:

113mIn; 131I

Therapeutic Radionuclides: - emitters: 32P; 47Sc; 64Cu; 177Lu; 188/186Re; 198Au; …. Auger/conversion e-: explored

67Cu; 89Sr; 90Y; 131I; 153Sm; 161Tb; 165Dy; 166Ho; 169Er; 170Tm; 175Yb;

125I;

103Pd;

117mSn;

and several others potential ones being

 emitters: 221At; 213Bi; 225Ac; 223Ra Thera(g)nostic Radionuclides/Surrogate Pairs: 64/67Cu; 44/47Sc; 99mTc/188/186Re; 86Y/90Y; 123/124/131I

Sealed Radioactive Sources: In ‗Teletherapy‘, the sealed sources used employ Co-60, a long lived (T1/2 5.64 years) high energy gamma emitter (E 1.33 and 1.17 MeV) and requires very high specific activity source to achieve high radiation flux for treatment. However, in ‗Brachytherapy‘ wherein the sealed radioactive source is placed within the body to treat the diseased area, a range of radioisotopes are used. In the past, radioactive wires, needles or seeds were used for brachytherapy treatment of localized approachable tumors such as uterine and breast cancers. With time, deep seated tumors such as in brain, prostate and liver* as well noncancerous ailments such as arthritic joints, skin warts etc. have been treated by brachytherapy. WORLD COUNCIL ON ISOTOPES

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*Liver cancers treated using radioactive particles or colloids do not fall clearly under ‗brachytherapy‘ as the radioactive material is not sealed. But they also do not fully fit under ‗radiopharmaceuticals‘ as the therapy is achieved merely due to its local position and not due to its chemical/biochemical characteristics. However, as the product is administered internally just as radiopharmaceuticals are, they are handled just as radiopharmaceuticals with respect to preparation, regulations etc.

While high energy gamma emitters of metallic radioisotopes Au-198, Ir-192 and to a limited extent Co-60 were used in the past (and continue to be used) the range has expanded now with low energy Auger/conversion electron emitters I-125 and Pd-103 seeds being used widely for prostate cancer treatment and several beta emitters for locoregional brachytherapy of joints, liver etc. (predominantly Y-90; and others such as Sm-153, Er-169, Lu-177, P-32, etc. and the isotope is chosen depending upon the size of lesion to be treated). The high LET of beta radiation and the ‗by-stander‘ cancer killing effect observed with particles are seen to be advantageous for therapy. The sealed radioactive source used for medical sterilization and preparation of novel materials for healthcare applications use Cobalt-60, nearly always. Co-60 or Cs-137 sources are used for irradiating blood before transfusion to patients, especially those with compromised immunity. Among the numerous radionuclides mentioned above, a large number are produced in research reactors.

Production of Radionuclides in Research Reactors: Research reactors were the main source of radioisotopes enabling radiation-based applications in large scales. As a variety of reactions induced by neutrons are possible, (such as radiative neutron capture (n, ); neutron capture followed by beta decay (n,); (n,p); (n,α); (n,f) ) there is a huge potential to produce a wide range of radioisotopes in reactors. However, although there are numerous radioisotopes for every element, only a small fraction of these are produced in a sustainable/feasible manner and used. The physiochemical properties (half-life, mode of decay, energy of radiation, amenability to label molecules) as well the production logistics are the important factors in this context. The feasibility of production of a radioisotope in a viable manner depends on the factors such as reaction cross sections, natural abundance of target nuclide, possible radionuclide impurities formed, separation and purification of the isotope of interest and the cost. Many

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radionuclides with attractive physical features have not reached clinical use because of unacceptable amounts of radionuclide impurities co-produced or unamenable chemistry.

The most widely used radioisotopes listed earlier, could be envisioned as clusters in the periodic table as depicted in the adjoining figure.

Many of the radioisotopes used in healthcare are produced in research reactors, and most often using (n,) or (n,) reactions. But, fission of U235 which results in a wide range of radioisotopes with varied yields, peaking around mass numbers 100 and 130, as shown in the adjacent figure, has been the route for production of Tc-99m and a few other radioisotopes such as I-131, Xe-133.

The following table gives the main routes of production of the commonly used reactor produced radioisotopes in healthcare.

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Commonly Used/Explored Reactor Produced Radioisotopes used in Healthcare RN

Half life

Reaction

32P

14.3 d

32S

47Sc

3.35 d

46Ca(n,γ)47Ca → 47Sc

(n,p)32P

Uses

Comments

Therapy – Nuclear medicine; brachytherapy Therapy – Nuclear Medicine

High energy 1n0 needed Currently limited use

Teletherapy; Radiation sterilization;

Huge amounts needed; produced in power reactors also; Co59 100% nat. abundance

Theragnostic pair of Sc-44; growing interest

47Ti(n,p)47Sc 60Co

5.27 y

59Co

(n, γ)60Co

67Cu

2.58 d

67Zn(n,p)67Cu

Therapy – Nuclear Medicine

Theragnostic pair of Cu-64; growing interest

89Sr

50.5 d

89Y(n,p)89Sr

Therapy– Nuclear Medicine

High energy palliation

90Y

2.7 d

235U(n,f) 90Sr

Therapy– Nuclear Medicine

Radionuclide Generator- big advantage; high potential for use

99mTc

6h

235U(n,f) 99Mo

Diagnosis– Nuclear Medicine

Therapy– Nuclear Medicine

Radionuclide Generator – big advantage Tc-99m – work horse of diagnostic NM (n,f) route yields very high specific activity Mo-99 which is preferred. Explored; but did not grow

Therapy– Nuclear Medicine

Explored; enriched target needed for use; did not grow

Diagnosis – Nuclear Medicine

Radionuclide generator; but low yields for production of Sn-113; did not grow much

Diagnostic – in-vitro assays Brachytherapy- prostate, eye Therapy– Nuclear Medicine

Gas irradiation facility needed; niche uses

Therapy-Brachytherapy Blood irradiation

Cs-137 is generally separated from irradiated spent fuel of a reactor

(-)90Y (-)99mTc

98Mo(n,γ) 99Mo(-)99mTc

105Rh

1.47 d

104Ru(n,γ) 105Ru

109Pd

13.7 h

108Pd

113mIn

1.7 h

112Sn(n,γ) 113Sn

125I

60 d

124Xe(n,γ) 125Xe

131I

8.0 d

130Te(n,γ) 131Te

(-)105Rh

(n, γ)109Pd (-) 113In (EC)

125I

(-) 131I ;

235U(n,f)131I 137Cs

30 y

235U(n,f) 137Cs

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1n0

needed; well established for bone pain

High specific activity from both routes; High yield through (n,f)

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Therapy– Nuclear Medicine

Explored; but did not grow.

152Sm(n,γ)153Sm

Therapy– Nuclear Medicine

Established use in bone pain palliation

2.4 h

164Dy(n,γ)165Dy

Therapy– Nuclear Medicine

Explored; but did not grow

166Ho

24.3h

165Ho(n,γ)166Ho

Therapy– Nuclear Medicine

Ho-165 100 nat. abundance; good potential; explored, but limited use

169Er

9.3 d

168Er(n,γ)169Er

Therapy– Nuclear Medicine

Explored; but limited use

170Tm

128.6 d

169Tm

Therapy– Nuclear Medicine

Explored; has potential to grow Tm-169 100% nat. abundance

175Yb

4.2 d

174Yb(n,γ) 175Yb

Therapy– Nuclear Medicine

Explored; but did not grow; enriched target needed

177Lu

6.7 d

176Lu(n,γ) 177Lu;

Therapy– Nuclear Medicine

Excellent RN for therapy; steep growth; Carrier free grade through Yb route; (n,γ) route also attractive due to high capture th when enriched Lu-176 is used Enriched Re-185 needed. Explored; but did not grow

143Pr

13.6 d

142Ce(n,γ) 143Ce

153Sm

1.9 d

165Dy

(-) 143Pr

(n,γ)170Tm

176Yb(n,γ) 177Yb→--177Lu

186Re

3.8 d

185Re(n,γ)186Re

188Re

17.0 h

186W(n,γ)187W(n,γ)188W

Therapy– Nuclear Medicine (-) 188Re

Therapy– Nuclear Medicine

187Re(n,γ) 188Re

192Ir

74 d

191Ir

198Au

2.7 d

197Au

223Re

(n, γ)192Ir;

Brachytherapy

(n, γ)198Au;

226Ra(n,γ)227Ra()223 Ac

Brachytherapy Therapy-Nuclear Medicine (-)

W-188/Re-188 generator convenient for use; W-188 production by successive 1n0 capture; extremely low probability and requires very high flux – currently feasible only in just a few RRs with high neutron flux Predominantly used in high dose rate therapy that need large amounts of high specific activity Ir-192 Au-197 100% abundance Alpha therapy-increased focus; but challenging to use

223Th(-)223Ra

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Vital Role of Research Reactors in the Supply of Medical Isotopes: The long list of radionuclides in the above table shows the important role of reactors in enabling the practice of nuclear medicine and radiation-based therapies. Further, this list is not exhaustive; research continues to identify and produce medical radionuclides in a sustainable manner. Although accelerators/cyclotrons could be used for radioisotope production, not all the important ones can be produced through charged particle reactions and even when possible, the cost and the amounts producible need to be considered for feasible regular production and use. In this context, ageing of the existing well performing reactors, which cater to a huge fraction of global demand, is a major concern. Long unplanned shutdowns and maintenance shutdowns of these old reactors pose challenges for smooth uninterrupted supply of medical isotopes. A crisis witnessed in the Mo-99 supply during 2007-2009 period due to the long unplanned shut down of reactors, attracted global attention, as Tc-99m derived from Mo-99 is the lifeline of diagnostic nuclear medicine. This crisis also exposed the weak points in the supply chain of radioisotopes, especially the lack of healthy support to the reactors for sustenance. The efforts taken by the OECD-NEA in this matter to bring all the stake holders from all the sectors and around the world, is noteworthy. In response, all the stakeholders in the supply chain of Mo-99-Tc-99 generator put concerted efforts to ensure sustained supply of Mo-99, which continues to date; and thanks to these efforts, currently Mo-99-Tc-99m supply is robust. (The publications on Supply of Medical Isotopes by OECD_NEA are available at the OECD website). This crisis also led to shifts in the mind-set of the users as well as producers in achieving quick immediate gains as well as long term preparations. The precious Mo-99-Tc-99m generators were used prudently to use every bit of Tc-99m and a re-look at production of Mo-99 by neutron activation route along with development of technologies to use low specific activity Mo-99 were triggered. Further, production of Mo-99 using cyclotrons was also explored successfully; but, the yields will not match the quantities attainable using the fission route, which underscores the need to ensure large scale productions in reactors. Some of the existing reactors spruced up either by complete refurbishment (BR2, SCK-CEN, Belgium) or augmented the production significantly (OPAL, ANSTO in Australia), with significant investment in the necessary infrastructure. However, many of the current reactors may come to the end of their lives and might need to be decommissioned due to ageing and non-compliance with the current safety and regulatory requirements. For long-term security of supply of reactor produced medical isotopes, new research reactors are necessary. Building new research reactors is not an easy solution in the current times and could be extremely challenging. Yet, it is very important to have new reactors to take the on production load in time to serve the world with the radioisotopes that play a

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crucial indispensable roles in management of healthcare, especially for patients with cancers or heart diseases. This has been recognized and many research reactors (to mention a few - FRM2-Germany; Jules Horowitz-France; MBIR-ROSATOM-Russia; RA-10Argentina+Brazil; MYRRHA-Belgium; PALLAS-Netherlands) are either in different stages of construction or garnering support/funds. The global directive to shift to using LEU in place of HEU and the revised regulations for radioisotope processing facilities add to the challenges in the radioisotope production and supply chain. It is relevant to mention that the IAEA has been supporting the reactor community to help address the various aspects, through publications, coordinated research projects, scientific meetings, and expert advices.

Conclusion: Radioisotopes have an unequivocal unique role in healthcare. Medical radionuclide production through research reactors is important and poised to continue for the time being, despite the challenges faced. Tc-99m remains the most used medical isotope with about 40 Million annual diagnostic scans performed globally using Tc-99m radiopharmaceuticals, which has remained steady with some marginal growth. Therapeutic nuclear medicine applications are growing fast and the trend is expected to continue. Most therapeutic radioisotopes are produced in research reactors and while the demand for well-established therapy isotopes such as I-131 remains high/growing, the demand for more recent ones such as Lu-177 is increasing steeply. To cater to the increasing demands, the existing research reactors have geared up and new reactors are planned. The experience has taught that secure sustained supply of medical radioisotopes is possible only with cooperation from all stake holders and adequate financial support to run the facilities/reactors. This calls for the right mind set, prudence, co-operation and willingness to share the cost among all concerned – the producers, users and the healthcare industry.

To Contents

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02. Isotope-related News Mining Medical Isotopes from Nuclear Waste A half hour north of Seattle in Everett, about 15 black barrels sit in a nondescript storage facility owned by the nuclear innovation company TerraPower. Each barrel is the size of a large trash can, around 110 L, and weighs over 350 kg. Just inside the thick shell is a layer of foam padding. Within that padding sits a heavy-duty container, which in turn encloses a steel pipe capped on each end. Inside the pipe is a screw-top aluminum can, which holds a thick plastic bag, which encases a glass vial about the size of a tube of toothpaste. That innermost glass vial holds half a gram of a yellow matter—a mixture of the radioactive elements uranium and thorium. These smidgens of material would normally have been disposed as nuclear waste by the US Department of Energy (DOE) and its partner in disposal, the nuclear waste management company Isotek. Instead, TerraPower requested the samples so that Latkowski and his colleagues can unpack the Russian dolls and extract a valuable medical isotope: actinium-225, which results from radioactive decay of uranium and has shown promise in treating a range of cancers. TerraPower hopes that mining the waste will yield between 200,000 and 600,000 doses of 225Ac a year, 100 times the number of doses currently available globally. TerraPower‘s efforts are part of a global push to increase actinium production to ensure a reliable supply for medical research and clinical use. To read more please visit: https://cen.acs.org/physical-chemistry/nuclear-chemistry/Mining-medical-isotopesnuclear-waste/98/i29 Source: c&en

How Research Reactors Help Make Medical Imaging Possible More than 80% of the medical imaging used each year to diagnose diseases like cancer is made possible by the pharmaceutical drugs produced, for the most part, in research reactors. These radiopharmaceuticals contain the radioisotope technetium-99m (99mTc ), which comes from the radioisotope molybdenum-99 (99Mo) that is primarily produced in research reactors. “While

99Mo

or even

99mTc

can be produced using other approaches, research

reactors are particularly cost-effective and well-suited to this, especially for commercial, large-scale production,‖ said Joao Osso, Head of the IAEA‘s Radioisotope Products and Radiation Technology Section. ―This is because they can produce large amounts of 99Mo with the right characteristics that make it WORLD COUNCIL ON ISOTOPES

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easy to extract 99mTc using a generator in a hospital, thereby keeping supplies of radiopharmaceuticals flowing consistently and reliably for more patients.‖ With the IAEA‘s support, SAFARI-1 has undergone continuous development and improvements since it began operation in 1965, including its conversion from high enriched uranium fuel to low enriched uranium fuel in 2009 (learn more about this kind of conversion) and its transition from high enriched to low enriched uranium targets, which was completed in 2017. These activities have helped to ensure better utilization of the reactor and its successful transition to more commercial use. To read more please visit: https://www.iaea.org/newscenter/news/how-research-reactors-help-make-medicalimaging-possible Source: IAEA

US Nuclear Partners MIFTI/MIFTEC Revolutionizing Cancer & Heart Disease Imaging & Cancer Radiation Treatment The creation and production of radioisotopes requires massive quantities of neutrons. Today‘s radioisotopes are made in the few reactors around the world, some of which are ageing and need replacement. The unforeseen shut-down of a couple of aged reactors last decade resulted in global shortage of radioisotopes. Although currently the security of supply of medical radioisotopes has been ensured through collective efforts from the reactor community, the need for copious neutron source is still there. History was made that could change the world when US Nuclear (UCLE: OTC) partners MIFTI and MIFTEC demonstrated their historic Fusion Energy breakthrough at the University of Nevada, Reno National Terawatt Facility where they repeatedly created over 10 billion neutrons per pulse on a 1 Million Ampere Staged Z-Pinch machine using low-cost isotope of hydrogen from common seawater as fuel. A product of common seawater, this fuel that powers US Nuclear partners MIFTI/MIFTEC is not only as abundant as all the oceans combined, but ONE GALLON OF SEAWATER PRODUCES THE SAME AMOUNT OF ENERGY AS 300 GALLONS OF GASOLINE. To read more please visit: https://seekingalpha.com/instablog/21922151-bioresearch-alert/5477362-us-nuclearWORLD COUNCIL ON ISOTOPES

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partners-mifti-miftec-revolutionizing-cancer-heart-disease-imaging-cancer Source: Seeking Alpha

The Nuclear Battery Aboard Perseverance, the Next-Gen Mars Rover NASA‘s next-generation Mars rover Perseverance, which successfully launched on July 30 atop an Atlas 5 rocket from the Cape Canaveral Air Force Station in Florida, will depend on a ―nuclear battery‖ for electrical power when it completes its seven-month journey to the Red Planet. Idaho National Laboratory (INL) celebrated the launch of the rover, and especially the Multi-Mission Radioisotope Thermoelectric Generator (MMRTG). MMRTGs essentially use radioisotope power systems (RPS) to convert heat from the natural decay of Pu-238 radioisotope into electricity. RPSs are ideal for space missions because they are compact, durable and reliable, providing continuous power over long periods of time as INL explained in a special feature on its homepage on Thursday. To read more please visit: https://www.powermag.com/the-nuclear-battery-aboard-perseverance-the-next-genmars-rover/ Source: POWER Magazine

Bruce Power, Cameco join Nuclear Innovation Effort Bruce Power and Cameco yesterday announced the launch of a center for next generation nuclear technologies as one of a series of initiatives to leverage their existing partnership to help rebuild the Canadian economy post-COVID, protect the environment and fight disease. The Nuclear Innovation Institute (NII) Centre for Next Generation Technologies will work to identify post-COVID economic, environmental and healthcare opportunities. Bruce and Cameco are founding members of the NII, an Ontario based not-for-profit organization set up in 2018 as a platform for accelerating innovation in the Canadian nuclear industry. The companies will also expand their role in medical isotope production. Cameco will use its facility in Cobourg, Ontario - location of it fuel manufacturing operations - to contribute to the development of a new isotope production system being developed by Bruce's partner Isogen to help produce lutetium-177 WORLD COUNCIL ON ISOTOPES

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In a separate announcement yesterday Isogen, a joint venture of Framatome and Kinectrics, said it is completing the final phase of engineering, testing and design for a mock-up of the system. Bruce Power aims to begin harvesting the isotope, which is used to treat prostate cancer and neuroendocrine tumors, in 2022. Cameco is also a key supplier of materials in the production of cobalt-60, which is produced by Bruce in partnership with Ottawa-based Nordion and is used to sterilize medical equipment as well as in cancer treatment. To read more please visit: https://www.world-nuclear-news.org/Articles/Cameco-and-Bruce-Power-partner-tosupport-nuclear Source: WNN

McMaster University to Spearhead Collaborative Project on Building a Resilient Canadian Medical Isotope Supply Chain In June, the Canadian Nuclear Isotope Council (CNIC) and Nuclear Innovation Institute (NII) announced a joint study to identify challenges facing Canada‘s medical isotope supply chain. Today that partnership took a major leap forward with McMaster University formally agreeing to lead the research and development of the project. Through this initiative, McMaster University will lead the project, defining its scope and undertaking the rigorous analysis while the CNIC and NII will provide oversight, direction and help the university connect with other critical stakeholder organizations that can assist with the project. The project will roll out over a multi-phased approach with the initial phase looking to place a value on the cost of supply chain disruptions to patients and the industry. To read more please visit: http://www.canadianisotopes.ca/mcmaster-university-to-spearhead-collaborativeproject-on-building-a-resilient-canadian-medical-isotope-supply-chain/ Source: Canadian Nuclear Isotope Council

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Nuclear Medicine Radioisotopes Industry Report Indicates Industrial Forecast, Growth Rate & Market Share 2026 The report features unique and relevant factors that are likely to have a significant impact on the Nuclear Medicine Radioisotopes market during the forecast period. This report also includes the COVID-19 pandemic impact analysis on the Nuclear Medicine Radioisotopes market. This report includes a detailed and considerable amount of information, which will help new providers in the most comprehensive manner for better understanding. The report elaborates the historical and current trends molding the growth of the Nuclear Medicine Radioisotopes market The research study on the Nuclear Medicine Radioisotopes market offers inclusive insights about the growth of the market in the most comprehensible manner for a better understanding of users. Insights offered in the Nuclear Medicine Radioisotopes market report answer some of the most prominent questions that assist the stakeholders in measuring all the emerging possibilities. To read more please visit: https://primefeed.in/news/3835694/nuclear-medicine-radioisotopes-industry-reportindicates-industrial-forecast-growth-rate-market-share-2026-covid19-impact-analysis-keyplayers-agfa-gevaert-group-braco-cardiarc-cardinal/ Source: primefeed

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03.Sketches from the Secretariat 3-1. KOICA-KAERI-WCI-IAEA Joint Training Course on Establishment of a LongTerm Management Plan by Strengthening Capacity for Diagnostic and Therapeutic Radioisotopes and Radiopharmaceutical Application from 2 to 13 November 2020 We are very pleased to announce that the KOICA-KAERI-WCI-IAEA Joint Training Course on Establishment of a Long-Term Management Plan by Strengthening Capacity for Diagnostic and Therapeutic Radioisotopes and Radiopharmaceutical Application will be held from 2 to 13 November 2020. This course will be hosted by the Korea Atomic Energy Research Institute (KAERI) in cooperation with the World Council on Isotopes (WCI) and will be organized by the Korea International Cooperation Agency(KOICA) in cooperation with the International Atomic Energy Agency(IAEA). The main objective of the 2020 course is to transfer crucial knowledge and practical skills to managerial or directorial level public officials in the participating target countries with the aim to support long term strategies for strengthening capacities, as well as policies for regulations in the diagnostic and therapeutic radioisotope and radiopharmaceutical applications‘ field. This course is being held over three consecutive years from 2019 to 2021 and took place over two weeks in 2019. It is to take place over another two weeks in 2020 and there will be one more week in 2021, too. The training courses for 2019 and 2020 have been based on lectures, discussions, practical activities, field trips, country reports, and action plans in principle. However, COVID-19 has led to changing the format of this course for 2020, utilizing e-learning techniques. Thus, the course format will be based on lectures, Q&A, country reports, and action plan activities. Thus it is strongly recommended that each participant prepares a place to become absorbed in his/her e-learning in their country (e.g. at the office, at home, etc.). In addition, those who participated in the programme from 2019 to 2020 should be participating in the programme planned for 2021. Therefore, the nomination of the participants for the 2020 course will mainly come from the countries that participated in the KOICA-IAEA Joint Training Programme on the Establishment of the Long Term Management Plan by Strengthening the Capacity for Diagnostic and Therapeutic Radioisotopes and Radiopharmaceutical Application held from 23 September - 4 October, 2019 in Seoul, Korea. WORLD COUNCIL ON ISOTOPES

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Qualifications and experience for participants are shown as follows: 1) Be proficient in English with good listening comprehension and communication skills 2) Be managerial or directorial level public officials in charge of the enactment of policies or regulations in the radiochemistry or radiopharmaceutical fields 3) Possessing at least a bachelor's degree in science/engineering; management qualifications will be an added advantage Applications must be received at the International Atomic Energy Agency, P.O. Box, A1400 Vienna Austria, no later than 10 September 2020. The target recipient countries are Argentina, Bangladesh, India, Macedonia, Malaysia, Mexico, Montenegro, Philippines, Serbia, and Thailand. Nominations for the training course should be submitted to the IAEA online through the Technical Cooperation Department‘s In Touch system (http://intouch.iaea.org). Should this not be possible, nominations may be submitted on the standard IAEA Nomination form for training courses (available on the IAEA website: http://www.iaea.org/). Completed forms should be endorsed by relevant national authorities and returned to the Agency through the official channels, i.e., the designated National Liaison Office for IAEA Matters. The final selection of course participants will be held jointly by the IAEA and communicated to KOICA, KAERI, and WCI. For more information, please visit the WCI website(www.wci-ici.org) to see the Prospectus of this training programme.

3-2. KAERI-WCI-IAEA e-Learning Course on Diagnostic and Therapeutic Radioisotopes and Radiopharmaceuticals Application from 30 November to 18 December 2020 (3weeks) We are pleased to announce that the KAERI-WCI-IAEA e-Learning Course on Diagnostic and Therapeutic Radioisotopes and Radiopharmaceuticals Application will be held from WORLD COUNCIL ON ISOTOPES

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30 November to 18 December 2020 (for 3 weeks). This course will be hosted by the Korea Atomic Energy Research Institute (KAERI) in cooperation with the World Council on Isotopes (WCI). The objective of this e-learning course is to strengthen then transfer crucial knowledge and practical skills to technical professionals in the radiopharmaceutical field. As a result, they can build the skills needed to manage radioisotopes and radiopharmaceuticals for diagnostic and therapeutic applications in their home countries. The e-learning course will take place over 3 weeks, and it includes a kick-off meeting, a closing meeting, lectures, Q&A, and assignments. E-learning is a type of learning that utilizes electronic technologies to access an educational curriculum outside of a traditional classroom. Thus it is strongly recommended that each participant prepares a place to become absorbed in his/her e-learning in their country (e.g. at the office, at home, etc.). The place should have equipment (e.g., a web-camera, a headset, software, a computer, an Internet connection, etc.) necessary to participate in the e-learning course. In addition, the organizers do not provide the participants with any auxiliary devices (e.g. CD (Compact Disc), USB flash drive, etc.). The participants should be qualified or experienced in the following: 1)Proficient in English with good listening comprehension and communication skills in order to actively participate in the training course without difficulties. 2)The applicants should be employed by governmental authorities, organizations, medical or R&D institutes, or regulatory bodies involved in the radiopharmaceutical field. However, medical technologists who operate radiological instruments are excluded from participation. 3)Possess at least a scientific or technical bachelor‘s degree. Nominations for the training course should be submitted to the IAEA online through the Technical Cooperation Department‘s In Touch system (http://intouch.iaea.org). Should this not be possible, nominations may be submitted on the standard IAEA Nomination form for training courses (available on the IAEA website: http://www.iaea.org/). Completed forms should be endorsed by relevant national authorities and returned to the Agency through the official channels, i.e., the designated National Liaison Office for IAEA Matters. Applications must be received at the International Atomic Energy Agency, P.O. Box, AWORLD COUNCIL ON ISOTOPES

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1400 Vienna Austria no later than 10 October 2020. The final selection of course participants will be held jointly by the IAEA and communicated to KAERI and WCI. The participants should cover all expenses (e.g., a web camera, a headset, software, a computer, an Internet connection, studio rental, etc.) necessary to participate in the elearning course. In addition, the organizers do not provide the participants with any auxiliary devices (e.g., CD (Compact Disc), USB flash drive, etc.). The organizers do not accept liability for the payment of any cost or compensation that may arise from damage or loss of personal property, illness, injury, disability, or death of a participant while travelling to and from, or when attending, the course. It is clearly understood that each organization, in nominating the participants, undertakes the responsibility for such coverage. There will be a selection of excellent graders who may have a chance to go to Korea for a 1-week Technical Visit to see the diagnostic and therapeutic radioisotope and radiopharmaceuticals applications. All costs (e.g., flight tickets, stipends, accommodation, etc.) will be supported. For more information, please visit the WCI website(www.wci-ici.org) to see the Prospectus of this training programme.

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04.Future Conferences and Events CRT 2020 – the 2nd China Radiation Technology Conference • Date: September 28 – 29, 2020 • Venue: Shanghai, China • Website: http://en.shcrtexpo.com/p/453665/ China Radiation Technology Conference is a comprehensive conference of Radiation Technology industry with great scale and widely influence, 10 fields are covered in the 2020 CRT: electron accelerator, isotope technique, radiation detection, radiation imaging, irradiation processing, instrumentation, nuclear medicine and molecular imaging, radiology, medical imaging AI, radiation protection and nuclear energy safety. As a professional expo, covering the whole industrial chain related to radiation technology, CRT mainly focuses on radiation technology display and communication about the industry trends and regulations in China. It will become the preferred platform for corporations to expand market channels and promote their brands.

RRFM2020 • Date: October 11 - 15, 2020 • Venue: Helsinki, Finland • Website: https://www.euronuclear.org/rrfm-2020-helsinki/ RRFM, the European Research Reactor Conference, is the annual gathering of the research reactor community in Europe. In 2020, we invite you to Helsinki, Finland. The conference program will revolve around a series of plenary sessions dedicated to the latest global developments with regard to research reactor technology and management. One of our keynote speeches will provide insights into the TRIGA fuel production restart at the Framatome CERCA facility. So, mark your diary, block 11 – 15 October in your agenda and join us in Finland!

EANM 20 • Date: October 22 – 30, 2020 • Venue: Virtual • Website: https://eanm20.eanm.org/ With more than 150 sessions, the European Association of Nuclear Medicine(EANM) Annual Congress is the most valuable Nuclear Medicine Meeting worldwide. Each year, nearly 7,000 participants have the possibility to network, socialize and discuss the newest trends and findings in the field of Nuclear Medicine. WORLD COUNCIL ON ISOTOPES

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12th World Congress on Analytical Chemistry and Instrumentation • Date: October 19 – 20, 2020 • Venue: Rome, Italy • Website: https://analyticalchemistry.alliedacademies.com/ Analytical Chemistry 2020 is delighted to invite all of you to the "12th World Congress on Analytical Chemistry and Instrumentation, booked for October 19-20, 2020 in Rome, Italy. Analytical Chemistry Congress - this gathering holds increasingly engaging sessions like symposiums, lectures, workshops (on an assortment of themes), publication introductions, and different programs for its members from anywhere in the world. It gives attendees the chance to meet and communicate with leading scholars, researchers, friends, colleagues, sponsors, exhibitors, and undergraduates from all over the globe. This general gathering allows for announcements on interesting examination results, new discoveries and utilitarian change understanding.

IRPA 15 • Date: January 18 – 22, 2021 • Venue: Seoul, Republic of Korea •Website: https://www.irpa2020.org/ International Radiation Protection Association‘s(IRPA) International Congresses are a major event in the world of radiation protection, and are held every four years. IRPA15 in Seoul, January 2021, will be the first such congress to be held in Asia since the Hiroshima Congress in 2000, and will be a great opportunity for radiation protection professionals from Asia and around the world to meet and discuss the key issues of our time.

2021 SNMMI Mid-Winter and ACNM Annual Meeting • Date: January 28 – 31, 2021 • Venue: San Francisco, California, USA •Website: 2021 SNMMI Mid-Winter and ACNM Annual Meeting The 2020 Society of Nuclear Medicine and Molecular Imaging(SNMMI) Mid-Winter and American College of Nuclear Medicine(ACNM) Annual Meeting offers you a focused meeting environment and tailored learning approach designed to further develop relevant skills and maximize tangible outcomes for your practice. Leading molecular imaging and nuclear medicine physicians, radiologists, cardiologists, pharmacists, scientists, lab professionals, and technologists, representing the world's top medical and academic institutions and centers.

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17th International Conference on Cancer Science and Radiation Oncology • Date: March 15 – 16, 2021 • Venue: Zurich, Switzerland • Website: https://radiationoncology.alliedacademies.com/ The 17th International Conference on Cancer Science and Radiation Oncology is aimed at creating a platform to express and exchange the thoughts and ideas on recent advancements in cancer treatment. The main focus of the conference will be on developing or innovating new techniques and methodologies for the next generation of cancer treatment.

Call for Papers: International Conference on Applications of Radiation Science and Technology • Date: April19 - 23, 2021 • Venue: Vienna, Austria • Website: https://www.iaea.org/events/icarst-2021 Interested contributors have until 31 July 2020 to submit abstracts for the Second International Conference on Applications of Radiation Science and Technology, which is to be held at the IAEA headquarters in Vienna, Austria, from 19 to 23 April 2021. ICARST-2021 will cover a variety of topics related to the applications of radiation technologies in fields as diverse as industry, medicine, materials science, engineering, biology, physics and chemistry. The conference will serve as a platform for fostering new initiatives among industry and academia, establishing new and strengthening existing collaborations and identifying best practices as well as raising awareness among decision makers on how radiation technologies can be applied to meet global challenges.

AwRI2020 • Date: May 31 – June 3, 2021 • Venue: Budapest, Hungary • Website: https://indico.cern.ch/event/820113/ Radioactive nuclei play a significant role in many current astrophysical pursuits, from the origin of the elements to the driving of emissions from supernovae (56Ni) and kilonovae (rprocess radioactivity). Radioactive nuclei are crucial for direct studies of galactic enrichment (7Be, 26Al, 44Ti, 60Fe, 99Tc, 244Pu) and stellar explosions (56Ni, 44Ti). Stars and their explosions, galaxies and their evolving interstellar medium, and the origin of the solar system are among the targeted astrophysical objects. Stardust, meteorites, ocean floor deposits, cosmic-rays, and gamma-ray spectroscopy provide a rich variety of astronomy WORLD COUNCIL ON ISOTOPES

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to exploit the inherent power of radioactivity. Investigation tools range from numerical models, astronomical instrumentation, and laboratory experiments to derive material compositions and nuclear reaction rates. The aim of the conference is to bring together researchers from all of these different fields to promote interaction through the common ground of radioactivity.

IRRMA 2021 • Date: June 4 – 9, 2021 • Venue: Moscow, Russia • Website: http://www.lnf.infn.it/conference/irrma2021/ The International Topical Meeting on Industrial Radiation and Radioisotope Measurement Applications(IRRMA) is a triennial event organized for the purpose of bringing together scientists and engineers from around the world who share an interest in radiation and radioisotope measurement applications.

IsoEcol 2021 • Date: June 20 – 26, 2021 • Venue: Gaming, Austria • Website: https://sites.google.com/view/isoecol2020/ The 12th International Conference on the Applications of Stable Isotope Techniques to Ecological Studies(IsoEcol) will be held in the beautiful town of Gaming, Austria, organized by the InterUniversity Center for Aquatic Ecosystem Research WasserClusterLunz in cooperation with the International Atomic Energy Agency (IAEA) from June 20-26, 2021. The conference venue is at the historic Kartause (Charter house) in Gaming (pronounced Gah-ming), approximately 2 hours from Vienna by car or public transportation.

ARIS 2021 • Date: September 5 - 10, 2021 • Venue: Palais des Papes, Avignon, France •Website: https://indico.in2p3.fr/event/19688/ ARIS 2020, the fourth international conference on Advances in Radioactive Isotope Science(ARIS), will be held in France's beautiful city of Avignon from 14-19 June 2020. ARIS is the flagship conference for rare isotope science, born from the merger of the international conferences ‗Exotic Nuclei and Atomic Masses‘ and ‗Radioactive Nuclear Beams‘.

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WCI Monthly Newsletter Call for Articles

The WCI Secretariat provides its Monthly Newsletter to about 1,600 subscribers worldwide. The WCI monthly newsletter is a communication channel for the dissemination of information among members and other interested parties in the field of isotope and radiation related technologies. For more and better information on isotopes production and application, the WCI Secretariat is cordially inviting your valuable contributions.

1. Contents WCI Monthly Newsletter covers the following and contributions are welcome for any of the following topics: 

Lead article: National policies, R&D outcomes, views of experts, current issues, innovative technologies in the field of radiation and radioisotopes

Conference report: Report on relevant conferences

Future Conferences: Any events (conferences/seminars/workshops) related to the field of radiation and radioisotopes

* Presenting events through the WCI Newsletter allows wider audiences to be informed, thereby potentially increasing participation. 

Isotope-related news: latest news related to the radiation and radioisotopes

My biz on isotopes: topics that demonstrate the cross-cutting and interdisciplinary technologies of WCI member organizations (Please refer to the previous edition (2016 Vol. 5 Issue 2) for more details)

* This column is an excellent opportunity to raise the profile of an organization and explore business opportunities with other WCI members.

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2. Requirements The article provider should be a member of the WCI. (To join us, please visit www.wciici.org and sign up online. There is no membership fee.) The writer should be a professional working in the field of isotope production or the application of isotopes or radiation. 3. Format All articles should be written in English. The length of article should be within 4 pages (A4, Verdana with 10 font size and 1.5 line spacing). Images may be included. All submissions meeting the above requirements should be submitted to secretary@wciici.org 4. Deadline Articles received by the WCI Secretariat via email before the 25th of the month will be considered for the next upcoming newsletter. 5. Others The WCI Publication Committee Chair will review articles for possible inclusion in the newsletter. Articles might be edited according to our own format. The WCI Secretariat will make payment for your lead article. It is KRW 100,000 per page A4 size (equal to US$85-95 per page)

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