Post on 28-Oct-2019
IAEA International Atomic Energy Agency
Status of Mo-99 Supply and New Developments
Joao Alberto Osso Junior Head, Radioisotope Products and Radiation Technology Section
IAEA 06 October 2015
IAEA
“The Agency shall seek to accelerate and enlarge the
contribution of atomic energy to peace, health and
prosperity throughout the world. It shall ensure, so far as
it is able, that assistance provided by it or at its request or
under its
supervision or control is
not used in such a way
as to further any military
purpose.”
The IAEA Mandate
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Contents
• Mo-99: importance, supply • IAEA structure and RPRT/ RR programmes • IAEA: HEU minimization • IAEA: stability of supply of Mo-99 • IAEA: Production of Tc-99m by Cyclotrons • IAEA: upcoming activities
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Mo-99 • Supply of Mo-99 • Tc-99m is the most important radioisotope for
diagnosis in Nuclear Medicine • Ideal decay properties: SPECT • Easy to label kits (> 20 kits) • Mo-99/Tc-99m generators • Fission produced Mo-99
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99mTc – radiopharmaceuticals
• Kits available for preparing 99mTc-radiopharmaceuticals to get info on
• Most organs – anatomy and abnormalities
• Most systems/dynamic – functional abnormalities
• ~ 30 M studies /year; work-horse of diagnostic nuclear medicine
• Cardiology; Oncology – Main areas
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Fission Production flow of Mo-99/Tc-99m
Source: www.covidien.com 7
Centralized Radiopharmacy
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Supply of Mo-99 crisis
• Supply problems since 2007 • Main shortage in 2009 • Ageing of Reactors • 2016: Nordion will cease
production: Extension of NRU operations until March 2018 as back-up capacity
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Current irradiators of U targets
Source: http://www.oecd-nea.org/med-radio/reports/sen-hlgmr2014-2.pdf 9
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Current processors of irradiated U targets
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Source: http://www.oecd-nea.org/med-radio/reports/sen-hlgmr2014-2.pdf
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Current irradiaton capacity and demand
• The annual growth rate of Mo-99 in mature markets (North America, Europe, Japan and the Republic of Korea) is assumed to be 0.5%, and in emerging markets 5%
• ORC: Outage Reserve Capacity
11 Source: http://www.oecd-nea.org/med-radio/reports/sen-hlgmr2014-2.pdf
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Current processing capacity and demand
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Source: http://www.oecd-nea.org/med-radio/reports/sen-hlgmr2014-2.pdf
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1. Mo-99 production routes: Nuclear reactors
“The supply of medical radioisotopes-Review of potential Molybdenum-99/Technetium-99m production technologies”. Nuclear Energy Agency-OECD November 2010
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1. Mo-99 production routes: Accelerators
“The supply of medical radioisotopes-Review of potential Molybdenum-99/Technetium-99m production technologies”. Nuclear Energy Agency-OECD November 2010
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Potental new irradiators
Source: http://www.oecd-nea.org/med-radio/reports/sen-hlgmr2014-2.pdf
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IAEA Organization for 99Mo Work
Office of the Director General
Department of Management
Department of Nuclear Science and Applications
Division of Physical and
Chemical Sciences
Radioisotope Products and
Radiation Technology Section
Department of Nuclear Energy
Division of Nuclear Fuel
Cycle and Waste Technology
Research Reactor Section
Department of Technical
Cooperation
Department of Nuclear Safety and Security
Department of Safeguards
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RR section
IAEA
Radioisotopes and Radiopharmaceuticals
• Availing Medical Radioisotopes (Mo-99/Tc-99m; Ge-68/Ga-68; Y-90; Cu-64 etc.)
• Development of Radiopharmaceuticals (Lu-177-anti-CD20) • Establishing production facilities – GMP/ regulatory compliant; training • Updating radiopharmaceutical monographs for the International
Pharmacopeia – WHO • Preparation of syllabus for the Radiopharmacy courses in recognized
Universities and e-learning modules for education and training in Radiopharmacy
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IAEA Priorities for 99Mo
HEU Minimization
Transition of 99Mo production away from
the use of highly enriched uranium (HEU)
Stability of Supply
Diversification of supply and movement to full
cost recovery to ensure the global demand is
met
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IAEA Activities on 99Mo
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• Collaboration with the OECD-NEA
• IAEA participates in the OECD-NEA’s High Level Group on the Security of Supply of Medical Radioisotopes (HLG-MR)
• Outreach of HLG-MR principles to Member States
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IAEA Priorities for 99Mo
HEU Minimization
Transition of 99Mo production away from
the use of highly enriched uranium (HEU)
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• Supported by US DOE-NNSA and the Government of Norway
• Series of meetings (since 2010) for key stakeholders to review progress, exchange information and explore opportunities for mutually beneficial collaboration
• Last meeting: 6 February 2015 • As the major producers are
progressing in their conversion activities, this group will re-direct its focus on addressing future activities that will assist producers following initial conversion
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4. Conversion of Major Mo-99 Producers to LEU
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4. Current processors of irradiated U targets
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Source: http://www.oecd-nea.org/med-radio/reports/sen-hlgmr2014-2.pdf
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IAEA Priorities for 99Mo
Stability of Supply
Diversification of supply and movement to full
cost recovery to ensure the global demand is
met
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Role of RPRT with RR • Stability of supply of Mo-99 in MSs • Indigenous production using non-HEU targets: 235U(n,f)99Mo reaction 98Mo(n,γ)99Mo reaction 100Mo(p,2n)99mTc reaction Cyclotron
• Small scale for local use • Regulatory aspects • New alternatives to Tc-99m • To assist MSs to improve operational
performance / reliability of an ageing fleet of RRs
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IAEA Activities on 99Mo
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• Small-scale, non-HEU production of 99Mo • A coordinated research project (CRP) on
“Developing Techniques for Small Scale Indigenous Molybdenum-99 Production Using LEU Fission or Neutron Activation.”
• CRP 2005-2011 • 14 Member States • LEU fission or (n,γ) reacion • IAEA Technical Report Series No. 478,
Feasibility of Producing Molybdenum-99 on a Small Scale Using Fission of Low Enriched Uranium or Neutron Activation of Natural Molybdenum (Jan 15) http://www-pub.iaea.org/MTCD/Publications/PDF/trs478web-32777845.pdf
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• EURASIA Coalition work • Reactors in Eastern Europe and
former Soviet states cooperating to produce low specific activity 99Mo via neutron capture of 98Mo (launched in 2008)
• IAEA Nuclear Energy Series No. NF-T-5-4: “Non-HEU Production Technologies for 99Mo and 99mTc” • Published 2013 • http://www-
pub.iaea.org/MTCD/Publications/PDF/Pub1589_web.pdf
3. Non-HEU Mo-99 production
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Small-scale, non-HEU 99Mo production
• Interregional Technical Cooperation Project INT1056 started in 2013 – PUI funds
• “Supporting the Global Deployment of Mo-99 Production Capacity for Nuclear Medicine Applications without the Use of Highly Enriched Uranium (HEU)”
• Aimed at assisting small-scale, national-level producers in setting up their production capability; • NOT aimed at creating commercial producers
• Will rely on LEU fission or n,gamma-based production • Open to any IAEA Member States wishing to receive
advice and assistance
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Small-scale, non-HEU 99Mo production
• Production infrastructure fact-finding missions were completed to Mexico, Morocco, Peru, Poland, and Romania. Similar missions were conducted in Egypt (2010) and Malaysia (2011)
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Training course
• Board of Radiation and Isotope Technology, BRIT • Mumbai, India • from 22 to 27 June 2015 • 15 participants → 12 countries • Member States:
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Algeria Bangladesh India Indonesia Kazakhstan Libya Malaysia
Peru Romania Thailand Uzbekstan Vietnam
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Training course
• Lectures, demonstrations and visits: Production and supply of Mo-99 All the aspects related to (n,gamma) production Generators with low specific Mo-99 (gel generator) Solvent extraction of Tc-99m Hot cells Regulatory issues
• Lecturers: Experts from India Ms. Yelena Chakrova, Head of Radiochemistry and Isotope
Production Center, Institute of Nuclear Physics AEC MINT, Kazakhstan
Joao Osso - IAEA 42
IAEA A. Celler, X. Hou, F. Bénard, T. Ruth, Phys. Med. Biol. 2011, 56, 5469
IAEA CRP - Accelerator-based Alternatives to Non-HEU production of Mo-99/Tc-99m (2011-2015): 100Mo(p,x)
Production of 99mTc in Cyclotron
PETtrace TR19 CP42 43
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11 Participating countries Target preparation (withstand heat
generated by the beam) Radionuclidic separation Mo/99mTc: fast
and high yield Recovery of the target: enriched and high
cost (supplier) Radionuclidic impurity: choose optimum
beam energy, time of irradiation and decay time
Delivery of 99mTc
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5. Main Issues
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TRIUMF announcement on January 5, 2015
6 hours irradiation time, 24 MeV, 450 µA 34 Ci of Tc-99m Clinical trials in Canada early 2015 Last RCM: 22-26 June 2015 (Vienna)
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5. Conclusions of the CRP
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• Alternatives for Tc-99m: Tl-201, Rb-82, F-18-Fluoride, Ga-68, Cu-64
• CRPs on: F-18 radiopharmaceuticals Ga-68 radiopharmaceuticals Production of Cu-64 and I-124
Role of RPRT
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New Activities
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• CRP on Sharing and Developing Protocols to Further Minimize Radioactive Gaseous Releases to the Environment in the Manufacture of Medical Radioisotopes, as Good Manufacturing Practice (2-28 August 2015)
• TM on New Ways of Producing 99mTc and 99mTc Generators (14-18 March 2016)
• TM on regulatory aspects of radiopharmaceutical production (07-11 December 2015)
• Support to TC projects (Regional LA 2016)
IAEA
The “1st International Conference on Applications of Radiation Sciences and Technologies – ICARST 2017” will be held in 24-28 April 2017 at IAEA HQ.
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