Excellence dedicated to nuclear medicine, healthcare and environment

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February 7th, 2019

The SMART project: accelerator based production of Mo-99

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Institute for Radioelements

Public Utility Foundation

No shares – no shareholder – no distribution of dividends Assets belonging to the foundation itself Under the tutorship of the belgian Government (e.g. : Board

members appointed by the Government for 6 years)

200 employees (Including its subsidiary IRE Elit)

Missions

Contribute to public health

Major worldwide producer of Mo-99 Worldwide first producer of I-131 Outstanding performance

Environmental protection

Continuous investment for innovation, modernization and safetyimprovements

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Located in Belgium

Strategic location for logistic Transport

Research Reactors

Other companies on site: Gamma sterilization : STERIGENICS

Transport : TRANSRAD

Our Site

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IRE

IRE ELiT

Innovation centre

Radiochemical products

Mo-99, I-131, Xe-133 for

medical useNon-processed products

Radiopharmaceutical products

Ga-68, Re-188 (Recent approval of file for MA in 13

countries in EU for Ga-68)

What we do

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LightHouse

The LightHouse project: ASML development project for equipment for the production of Mo-

100(g,n)Mo-99

Nationaal Icoon for ASML end 2016

ASML :

• Lithography equipment manufacturer for the semi-conductor industry

• Developed a free electron laser to generate EUV light for their lithography machines. A free electron laser is based on an high energy electron beam

• Discovered in 2015 that their new high energy electron beam could also be used to produce the radioisotope Mo-99

• Accelerator for Mo100 (g,n) Mo-99 reaction Specific Activity: up to 250Ci/g

Existing generators could be used

Mo-99m is used as a radioactive tracer in medical imaging technology mainly for diagnoses (SPECT) in cardiology, oncology and neurology.

The LightHouse production method based on a high power superconductive linear electron accelerator.

A superconductive accelerator is innovative versus the “standard” endeavors with electron accelerators: it allows for the combination of high volume and high quality production.

This accelerator produces a high energy electron beam with a high current. The high energy electrons are stopped in the target and produce Bremsstrahlung (gamma-rays or γ-rays transmute Mo-100 into Mo-99).

SPECT scan High levels of Tc-99m in pelvis and axilla (red) showing areas of cutaneous T-cell lymphoma.

Production of Mo-99 with super-conducting electron accelerator has potential to be at acceptable cost, Uranium free and to create limited waste

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Current production process with 50 year old reactors

Uranium target production

Reactor irradiation

Uranium target processing

GeneratorRadio-

Pharmacy /Hospital

Reactor Mo-99/Tc-99m production

Risk of proliferation

Aging reactors

Nuclear waste

Current production process with fission reactors

• Radio-isotopes (Mo-99/Tc-99m) are needed for cardiology or cancer diagnosis of 35 million people annually

• Reliability is of prime importance.

• Installation from early 70th

• New installations • Fission process

• Alternative process

Production process with accelerator using EUV-FEL modules

Uranium target production

Reactor irradiation

Uranium target processing

GeneratorRadio-

Pharmacy /Hospital

Reactor Mo-99/Tc-99m production

Mo-100 target production

Acceleratorirradiation

Mo-100 target processing

GeneratorRadio-

Pharmacy /Hospital

Accelerator Mo-99/Tc-99m production

Accelerator &Mo-100 target processing

(ASML)

Risk of proliferation

Aging reactors

Nuclear waste

No risk of proliferation

Innovative accelerator

Negligible waste

Production process with accelerator using EUV-FEL modules

Production process with accelerator using EUV-FEL modules

Uranium target production

Reactor irradiation

Uranium target processing

Reactor Mo-99/Tc-99m production

GeneratorRadio-

Pharmacy /Hospital

Mo-100 target production

Acceleratorirradiation

Mo-100 target processing

Accelerator Mo-99/Tc-99m production

Accelerator &Mo-100 target processing

(ASML)

Risk of proliferation

Aging reactors

Nuclear waste

No risk of proliferation

Innovative accelerator

Negligible waste

GeneratorRadio-

Pharmacy /Hospital

Production process with accelerator using EUV-FEL modules

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LightHouse

Partners and theirs roles ASML :

• World top in technology development - excellent innovators

• In charge for the technology development

– Development de technology and collaboration with specialists

– Concept Development of the concepts 2014-2016

– Lead System Architect

– System integration

IRE : leading the project

• World leader in radio-isotopes development, production and sales

• Market knowledge – final products and production technology

– Chemical processed development

– Evaluation of the current generators and the final product

– Building development

– Responsible for the different authorization processes

Let’s follow first an electron

• Electrons are released in the injector

• They are accelerated to 75 MeV in the super-conducting boosters

• The beam is split to approach the target from two sides

• In the exposure cell the high energy electrons are stopped in the Mo-100 target and produce Bremsstrahlung (gamma-rays or γ-rays) which transmute Mo-100 into Mo-99

• The target is cooled as the electrons create alsoa high thermal load on the target

• After exposure of the target during a week, part of the target is harvestedand processed to create the Active PharmaceuticalIngredient (API) Mo-99

Injector

Super-conductingboosters

Beam splitter

Exposure cell

Processcell

Cryo-plant

Life of an electron : from injector to API Mo-99

Injector

Super-conductingboosters

Beam splitter

Exposure cell

Processcell

• Bunches of electrons are released from the photo-cathode of the injector by laser pulses at a frequency of 1.3 GHz.

• These electron bunches are pulled away from the cathode by an electrostatic field of 350 kV.

• This results in a high brightness electron beam that has been demonstrated at more than 40 mA.

• This injector was built at CornellUniversity where it is now in operation.

Developed by

Cryo-plant

Injector: the source of the electrons

Injector

Beam splitter

Exposure cell

Processcell

Cavity

5 m

• A super-conducting booster allows for accelerating a large stream of electrons that is needed for high volume production of API Mo-99.

• Boosters are cooled with liquid Helium from a cryo-plant.

• Design of Cornell University

Developed by

Super-conductingboosters

Cryo-plant

Super-conducting Booster accelerates the electrons

Injector

Super-conductingboosters

Beam splitter

Exposure cell

Processcell

Beam B

Beam A

Beam B

Beam A

Developed by

• For high volume and high quality (Specific Activity) production of API Mo-99 it is proposed to expose the target from two sides. Therefore the beam is split.

• Both beams are transported towardsthe target by an achromatic arc.

• Fast scanning (1 MHz) over thetarget allows for uniformthermal load.

Cryo-plant

Beam splitter to expose target from both sides

Injector

Super-conductingboosters

Beam splitter

Exposure cell

Processcell

Developed by

Cryo-plant

Processcell

Exposurecell

The electron beam impacts on the target in the Exposure cell while API Mo-99 is prepared in the Process cell

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Project planning

Planning6 February 2019

Phase 2015 2016 2017 2018 2019 2020 2021 2022 2023 2024 2025 2026

1. Feasibility study

2. Forming consortium

3. Preparation:Risk mitigation,

4. Design & engineering

5. Manufacturing

6. Installation & commissioning

7. Pilot production

8. Commercial production

9. Install & com 2nd line 2026-2028

“feasible”

Technical Specs ready

Start commissioning

Supplier LOI signed

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3

Milestones“are we on track towards target?”

Milestones“are we on track towards target?”

Risk mitigatedOrganization in place

Risk assessment &de-FEL-inization

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Financing Risk mitigation

Start pilot production

Commercial production

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Questions / Discussion

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