status of mo-99 supply and new developments · 2016. 8. 9. · 1. mo-99 production routes:...

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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Demand of Mo-99 • 10,000 6-day Ci per week (world) • 5,000 6-day Ci per week (USA)

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Fission Production flow of Mo-99/Tc-99m

Source: www.covidien.com 7

Centralized Radiopharmacy

http://www.covidien.com/

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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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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


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Potential new processors

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Potential new producers – Australia

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Potential new producers – Rep. Korea

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Potential new producers - Argentina

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Potential new producers - Brazil

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Potential new producers – USA SHINE

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Potential new producers – USA SHINE

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Potential new producers – USA NorthStar

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New high capacity adsorber– PermaFix

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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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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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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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http://www-pub.iaea.org/MTCD/Publications/PDF/Pub1589_web.pdf



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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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100Mo(p,2n)99mTc

101Tc p n

n

100Mo

99mTc

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Cyclotron Production of Tc-99m

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Cyclotron Production of Tc-99m

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Demonstrating Proof of Concept

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Courtesy : Tom Ruth, Triumf, Canada

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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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99gTc 97gTc

95gTc

94gTc

93gTc

100,9xMo(p,2n)9xTc series

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5. Radionuclidic Impurities

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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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Potential new producers – Canada

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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.

Conferences

IAEA International Atomic Energy Agency

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status of mo-99 supply and new developments · 2016. 8. 9. · 1. mo-99 production routes:...

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