IAEA assistance in RI production and supply: 99Mo case

Joao Alberto Osso JuniorHead, Radioisotope Products and Radiation Technology

SectionNAPC/NA/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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IAEA Organization – RPRT Section

Office of the Director General

Department of Management

Department of Nuclear Energy

Department of Nuclear Science and Applications

Division of Physical and Chemical Sciences

Radioisotope Products and Radiation 

Technology Section 

Department of Technical 

Cooperation

Department of Nuclear Safety and 

Security

Department of Safeguards

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Nuclear Sciences & ApplicationsContribute to…

Promoting food securityand sustainable 

agricultural development

(FOOD & AGRICULTURE, 

NAFA)

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Improving the diagnosis and treatment of diseases andnutrition(HUMAN HEALTH, NAHU))

Making more, and cleaner water available to 

more people(WATER RESOURCES, NAPC)Understanding 

and protecting the environment 

(ENVIRONMENT LABORATORIES, NAEL)

Providing knowledge & expertise forscience & industry(RADIOISOTOPEPRODUCTION & RADIATION TECHNOLOGY, NAPC)

Sustainable Development Goals

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SDG #3: Good Health and Well-Being Building capacities in radiation sterilization of medicalproducts (radiation technology) Ensuring the right “dose” is provided to the patients

and products (radiation dosimetry) Improving diagnosis and treatment of cancer and chronic diseases;

diabetes, CVDs (diagnostic imaging; radiotherapy;nuclear medicine; radiopharmaceuticals) Contributing to better nutrition (stable isotopes) Controlling vector of human diseases (human sleeping sickness, malaria,

dengue, chikungunya and zika) (sterile insect technique)

SDG #9: Industry, Innovationand Infrastructure Enhancing capabilities in non-HEU and accelerator based technologies

for production of radioisotopes (accelerator; medical cyclotrons)

Facilitating availability of radiopharmaceuticals for cancer/NCDs patients (radioisotopes; radiopharmaceuticals)

Supporting capacity to apply radiation technologyfor health care, food safety, cleaner industrial processes and better environment

Enhancing capabilities in radiotracers and radiation based non-destructive testing for increased efficiency in industrial processes (radiotracers; NDT)

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Serving Member States: How?

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Applied R&D

• 12 NA labs• >20 Collaborating Centres• >100 Coordinated

Research Projects per year

Valid

atio

nTechnology

Transfer

• TECHNICAL COOPERATION PROGRAMME

• >130 LMI Member States• €39.95 million in 2015 (NA)

Provision of Services

• Dosimetry• Plant varieties;

insect strains• Audit missions• Reference

materials

Education and Training

• Guidelines; curriculum• E-learning• >400 trainees per year (NA labs)

Programme 2.5 Radioisotope Production and Radiation Technology

Programme description/objectives

Programme 2.5Radioisotope

Production and Radiation Technology

Sub-programme 2.5.1: Radioisotope Products for Cancer Management and non-Communicable

Diseases

2.5.1.001 Development and production of medical 

radioisotopes

2.5.1.002 Development of diagnostic and therapeutic 

radiopharmaceuticals 

Sub-programme 2.5.2: Radiation Technology

for Health Care and Industrial Applications

2.5.2.001 Industrial applications of radioisotopes and radiation techniques 

2.5.2.002 Radiation technologies for health care 

and environmental applications  

IAEA Projects

The IAEA can assist Member States in their work through various types of activities. These include: • Coordinated Research Projects (R&D) 13• Technical Cooperation Projects (implementation) 150• Regular program activities

– Networks and coalitions– Participation in complimentary, international activities– Meetings / Conferences– Missions– Publications– General Conference side-events and Scientific Forum– Collaborating Centres

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Radioisotope production

Radiopharmaceutical production

Diagnostic or therapeutic application

Cyclotrons Research reactor

Radionuclidegenerator

Hot cell

Synthesismodule

Layout

Availing medical radioisotopes Therapeutic Radiopharmaceuticals Labelled with New Emerging Radionuclides (67Cu,

186Re, 47Sc) – New CRP - 2016 Development of radiopharmaceuticals

Development and preclinical evaluations of therapeutic radiopharmaceuticals based on Lu-177 and Y-90 labeled monoclonal antibodies and peptides

Nanotheranostic: nanosized delivery systems for radiopharmaceuticals New CRP: Cu-64 Radiopharmaceuticals for Theranostic Applications – November 2016

Education (e-learning, training modules, sylabus for Universities) Regulatory issues: Due to the increasing complexity of radiopharmaceutical preparations

and the mandatory requirement of patient’s safety, there exists a widespread demand tosupport regulators and preparation of guidelines of Good Manufacturing Practice (GMP)

Updating radiopharmaceutical monographs for the International Pharmacopeia – WHO Publications

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Projects

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The case of Mo-99

Radioisotope production technologies

Nuclear EnergyNuclear Fuel

Cycle and Waste Technology

Research Reactors

Nuclear Applications

Physical and Chemical Sciences

Radioisotope products

Physics- RR Applications

Human Health Nuclear Medicine

IAEA Organization for Mo-99 Activities

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IAEA’s Mo-99/Tc-99m related activities

• Stability of supply of Mo-99 in Member States• HEU minimization• Indigenous production using non-HEU targets• Small-scale production of Mo-99 or Tc-99m for

local use and associated regulatory aspects• Coordination and participation in the OECD-

NEA’s HLG-MR• New alternatives to Tc-99m

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Reports• OECD-NEA: http://www.oecd-nea.org/cen/docs/2016/sen-hlgmr2016-2.pdf• Committee on State of Molybdenum-99 Production and Utilization and

Progress Toward Eliminating Use of Highly Enriched Uranium; Nuclear and Radiation Studies Board; Division on Earth and Life Studies; National Academies of Sciences, Engineering, and Medicine: https://www.nap.edu/catalog/23563/molybdenum-99-for-medical-imaging

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Technical Cooperation Projects

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Relevance to the TC Programme54 Technical Cooperation projects in the

field of radionuclide and radiopharmaceutical production for

medicine are supported by Radioisotope Products and Radiation Technology Section.

This number is expected to continue to increase according to trends observed in

the last decade.Regional LA 2016: Peru, Chile, Mexico

Coordinated Research Projects

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Developing Techniques for Small Scale Indigenous Molybdenum-99 Production Using LEU Fission or Neutron Activation (n, )

• 2005-2011

• 14 Member States

• 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”

• http://www-pub.iaea.org/MTCD/Publications/PDF/trs478web-

32777845.pdf

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• 2011-2015

• 18 participants from 16 Member States

• Production of Tc-99m in cyclotron - very successful: 6 hours irradiation time, 24 MeV, 450 A: 34 Ci of Tc-99m

• Clinical trials under way; regulatory approvals sought

• Self-sufficiency in hospitals/towns/country

• Good option for hospital or radiopharmacy; local productions

• Target specifications; reuse of targets etc. need consideration

Accelerator-based Alternatives to Non-HEU production of Mo-99/Tc-99m

Comparison of cyclotron- and reactor-based Tc-99m pertechnetate for the Univ. of Alberta Clinical

Trial (cancer thyroid patients imaged post-thyroidectomy) 23

Sharing and Developing Protocols to Further Minimize Radioactive Gaseous Releases to the Environment in the Manufacture of Medical Radioisotopes, as GMP

• 2014 - ongoing• Initiated as result of a request from a

five Member States - May 2014• First Research & Coordination Meeting -

August 2015• Second Research & Coordination

Meeting – planned 1Q 2017• Participants and observers from

Australia, Belgium, Canada, France, Germany, Indonesia, The Netherlands, Pakistan, Poland, Rep. of Korea, USA.

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New Ways of Producing Tc-99m and Tc-99m Generators

• Planned new CRP for 2017• Recommendation from Technical

Meeting on same topic (March 2016)• Aimed as use of low specific activity

Mo-99 for generator preparation and accelerator production of Tc-99m

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Training Events / Missions

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Supporting the Global Deployment of Mo-99 Production Capacity for Nuclear Medicine Applications without the Use of HEU

• Started 2013

• Aimed at assisting small-scale, national-level producers in setting up their production capability

– NOT aimed at creating commercial producers

• Supports LEU fission or n, -based production

• Expert missions to Mexico, Morocco, Peru, Poland and Romania (Egypt and Malaysia conducted earlier)

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• India (Board of Radiation and Isotope Technology)– 22-27 June 2015– 15 participants from 12 MS – Lectures, demonstrations and visits:

o Production and supply of Mo-99o Aspects related to (n,gamma) productiono Generators with low specific Mo-99 (gel generator)o Solvent extraction of Tc-99mo Hot cellso Regulatory issues

• Kazakhstan (Institute of Nuclear Physics)– Planned for 2017, in tandem with the closing of the round robin activity

• Round Robin Workshop– To explore the use of Tc-99m radioactivity concentration units and high capacity

absorbers for Mo– Planned for 2017

Interregional Training Courses & Workshops

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Objectives:• Assist in organization of Round Robin for Mo-99 production by 0n1 capture• Promote non-HEU production pathways• Facilitate estimates for local supply of Mo-99Means:

• Provision of samples and procedures• Advice and evaluation by international experts• Irradiation results analysis, both individual & group• Follow up workshops• Expert missions to identified labs

Mo-99 production by (n,) – Round Robin

Results:• 16 RR facilities• Analysis - December 2015 workshop• Demonstrated that ~1-3Ci/g specific saturation

activities with flux of 1x1014 cm-2s-1

• Summary paper accepted for publication in the Journal of Radioanalytical and Nuclear Chemistry

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Thematic Technical Meetings

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Global Capabilities for the Production and Manufacture of Molybdenum-99 Targets

• 20-21 October 2015• 31 participants from 15 Member States + EU Commission• Objectives:

• Discuss current and upcoming techniques and capabilities for the manufacture of targets used in the production of Mo-99

LEU foil target (USA) Irradiation baskets (Belgium)

Target holder and plates (Korea)

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Regulatory Aspects of Radiopharmaceutical Production• 7-11 December 2015• 9 participants from 8 Member States• Objectives and recommendations:

To share experience of current radiopharmaceutical regulation status in participating MSs;

To define a work plan for IAEA to support MSs that require assistance in this issue, in the form of education, training and harmonization tools;

To evaluate the need for an IAEA publication with recommendations of how new facilities or those that need renovation can comply with national regulations.

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New Ways of Producing Tc-99m and Tc-99m Generators

• 14-18 March 2016• 17 participants from 8 Member States• Objectives:

• Evaluate alternative routes for the production of Tc-99m and Mo-99• Evaluate optimization of available generators• Evaluate current status and potential development of Mo-99/Tc-99m generators using

low specific activity Mo-99

• Recommendations:• Round-robin• Training course • New CRP • Publication

• Concerns• Supply of enriched Mo target materials• Regulatory issues

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IAEA Publications

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Publications on Mo-99/Tc-99m

Publication in progress Reference Plan for Self Sufficiency in the 

Supply of Selected Radioisotopes Produced in Research Reactors: Latin America Case Study

CRP on the production of Tc‐99m by cyclotron

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Conferences & Upcoming Activities

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Upcoming IAEA Conferences

• Special Plenary Session on 12 Oct.• Session VI : Radiopharmacy

• Kevin Charlton – OECD role (HLG-MR)• Sally Schwarz – GMP in US (FDA; IND)• Adriano Duatti – Cardiac agents (Tc-99m, Tl-201 & PET)

IMIC 2016 (Oct 10-14, 2016)

2019 – International Symposium on Trends in Radiopharmaceuticals (approved) proposed date 06-10 May 2019

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The “1st International Conference on Applicationsof Radiation Sciences and Technologies – ICARST2017” will be held in 24-28 April 2017 at IAEA HQ.

Conferences - RPRT

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