Confidential

LightHouseProduction of radio-isotopes with a

super-conducting electron accelerator

Patrick de Jager – Director New Business

October 2017

Radio-isotopes with medical application

The accelerator

The exposure cell

30 October 2017

Slide 2

Confidential

Radio-isotopes with medical application

The accelerator

The exposure cell

30 October 2017

Slide 3

Confidential

Periodic table of elementsWhat is an isotope?

Source: Wikipedia

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Slide 4

SPECT (Single Photon Emission

Computed Tomography) with radioactive

Tc-99m

Brachytherapy of prostate cancer

with radioactive I-125

Diagnostic and therapeutic medical applications

Source: Ref 15, 51

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Slide 5

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Slide 6

SPECT CT image of left vertricle of the heart

Developed by

Types of radio-isotopes and demand

Isotope Worldwide

demand

[Ci/year]

Cd-109 10

Cu-67 3,000

F-18 150,000

I-123 2,000

I-125 1,000

I-131 22,000

Ir-192 28,000

P-32 10

Pd-103 3,000

Re-86 8,000

Re-188 18,000

Ru-82 30

Sm-153 14,000

Sr-189 800

Tc-99m 600,000

Tl-201 3,000

Y-90 2,600

Demand of commonly used radio-isotopes is mainly

Tc-99m (Technetium)

Other significant demand from F-18 (Fluor), Ir-192

(Iridium), I-131 (iodine) and Re-188 (Rhenium)

30 October 2017

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Slide 7

Cd-109

Cu-67

F-18

I-123

I-125

I-131

Ir-192

P-32

Pd-103

Re-186

Re-188

Ru-82

Sm-153

Sr-89

Tc-99m

Tl-201

Y-90

SPECT scan

High levels of Tc-99m in pelvis and axilla (red)

showing areas of cutaneous T-cell lymphoma.

Tc-99m

injected6 hr half-life

SPECT scannerdetects gamma photon emitted

by decay of Tc-99m

Generatortransport to hospital

decay of Mo-99 to Tc-99m

Mo-9966 hr half-life

30 October 2017

Confidential

Slide 8

Radio-isotopes are needed for cardiology or cancer

diagnosis and treatment of 60 million people annually

Reliability is of prime importance.

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Slide 9

Confidential

Current production process with 50 year old reactors

Uranium target

production

Reactor

irradiation

Uranium target

processingGenerator

Radio-

Pharmacy /

Hospital

Reactor Mo-99/Tc-99m production

Non-

proliferation

50 year old

reactors

Nuclear

waste

1. 3.2 Alternative production flows

Reactor

Electron

accelerator

Proton

accelerator

Deuteron

accelerator

HEU

LEU

Molybdenum

e,g target

p,n target

direct

D,n target

U-235

U-235

Mo-98

U-235 or

Th-232

Mo-100

U-235 or

Th-232

Mo-100

Mo-100

U-235

Mo-100

Mo-99

Mo-99

Mo-99

Mo-99

Mo-99

Mo-99

Mo-99

Mo-99

Mo-99

Tc-99m

Tc-99m

Tc-99m

Tc-99m

Tc-99m

Source: Ref 19,33, 152

A

B

C

D

E

F

G

H

I

J

(n,f)

(n,f)

(n,g)

(g,f)

(g,n)

(n,f)

(n,2n)

(p,2n)

(n,f)

(n,2n)

reaction

p=proton, n=neutron, f=fritting, g=gamma photon No fission

Fission based process

30 October 2017

Confidential

Slide 10

Zr-96 Mo-99K (alpha,n)Alpha

acceleratorAlpha beam Tc-99m

Production physics

Use of 35-60 MeV electrons to make very hard X-rays via Bremsstrahlung radiation

At higher energy unwanted reaction can happen resulting in Zircon-89 and Yttrium-

87 when using natural Molybdenum. These contaminants are not present when

using enriched Mo-100 targets

Mo-100 Mo-99

n

(g,n)

Source: Ref 1, 16, 23, 108, 109

30 October 2017

Confidential

Slide 11

30 October 2017

Slide 12

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Production process with accelerator using EUV-FEL modules

Uranium target

production

Reactor

irradiation

Uranium target

processingGenerator

Radio-

Pharmacy /

Hospital

Reactor Mo-99/Tc-99m production

Mo-100 target

production

Accelerator

irradiation

Mo-100 target

processingGenerator

Radio-

Pharmacy /

Hospital

Accelerator Mo-99/Tc-99m production

Accelerator &

Mo-100 target processing

(ASML)

Non-

proliferation

50 year old

reactors

Nuclear

waste

Not radio-

active

Innovative

acceleratorNegligible

waste

30 October 2017

Slide 13

Confidential

Production process with accelerator using EUV-FEL modules

Uranium target

production

Reactor

irradiation

Uranium target

processing

Reactor Mo-99/Tc-99m production

Mo-100 target

production

Accelerator

irradiation

Mo-100 target

processing

Accelerator Mo-99/Tc-99m production

Accelerator &

Mo-100 target processing

(ASML)

Non-

proliferation

50 year old

reactors

Nuclear

waste

Not radio-

active

Innovative

acceleratorNegligible

waste

Generator

Radio-

Pharmacy /

Hospital

No cost for

nuclear waste

ASML has involved many partners in feasibility study “Production of radio-isotopes with an electron accelerator”

Mo-100 target

production

Accelerator

irradiation

Mo-100 target

processingGenerator

Radio-

Pharmacy /

Hospital

Technical results of the feasibility study have been reviewed with all parties

30 October 2017

Confidential

Slide 14

Accelerator

Electron

source

Mo-100

exposure chamber

Processing

chamber

Conclusions feasibility study

Electron accelerator is feasible production method for Mo-99/Tc-99m

Commercial feasibility• Full cost 30% lower than with

nuclear reactor (NRG modelling)

• Investment of 65 MEuro per

beamline depreciated in 20 year

• Financing by consortium

Technical feasibility• Production volume

of 2 beamlines similar

to HFR: 200.000 6d-Ci/yr

• Existing generators can be

used

• Accelerator using modules of

ASML FEL

• Production of other radio-

isotopes is possible

Durability• Installation intrinsically safe

• Minimal nuclear waste generated

since production with electron

accelerator is very specific

• Modelling shows quality of

Mo-99 meeting requirements

Social importance• Medical need: Supply

guaranteed in consortium with

Generator Manufacturer(s)

• Employment: Potential

continuation of employment

with consortium including build

and operations of facility

Political importance• Investments are 4x lower

for production of radio-

isotopes with electron

accelerator than for

nuclear reactor

• Location of electron

accelerator and production

of radio-isotopes open for

discussion and depending

on consortium members

Next steps• Experimental

verification

• Create consortium

with Generator

Manufacturer(s)

• Start of production

possible by 2020

30 October 2017

Confidential

Slide 15

Radio-isotopes with medical application

The accelerator

The exposure cell

30 October 2017

Slide 16

Confidential

Technical feasibility

Accelerator using modules of ASML Free Electron Laser

Accelerator

Electron

source

Mo-100

exposure chamber

Processing

chamber

52 m

10 m

“Kicker”

Beam splitter

• Components in isotope accelerator are the same as designed for EUV-FEL

• Laser induced injector generates beam of 30 mA

• Super-conducting linear accelerator accelerates electrons to 60 MeV

• “Kicker” beam splitter and transport optics split the beam such that Molybdenum target is exposed from both sides Developed by

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Slide 17

Isotope beamline

RF cavity (1)

InjectorSolenoid

Initial Beam

shaper

Screen

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Slide 18

RF gravity (sections)

30 October 2017

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Slide 19

Isotope beamline

Deflector

Screen

RF cavity (5)

Sectorbend

Quadrupole

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Slide 20

Isotope beamline

Sector bend

Quadrupole

Sector bend

30 October 2017

Confidential

Slide 21

Radio-isotopes with medical application

The accelerator

The exposure cell

30 October 2017

Slide 22

Confidential

The yield challenge

Three conflicting challenges

have to be addressed

simultaneously in the design

of the exposure cell

The Thermal Challenge• Beam of > 1MW deposited in

Molybdenum

• Molybdenum should not melt

• Maximum cooling 30 W/mm2

• Design drives towards:

• Lower beampower

• More Molybdenum

• Enlarge Mo surface

The Specific Activity Challenge• Loading state-of-art generator with

certain capacity of Mo-99 requires

minimal Specific Activity

• SA should be >130 Ci/gram (End

of Exposure)

• Design drives towards:

• Longer exposure

• Less Molybdenum

The Yield Challenge• Sufficient production of Mo-

99 should be realized to

justify investments

• A beamlines should produce

100.000 Ci/yr (6d EoP)

• Design drives towards:

• Shorter exposure

• Higher beam power

30 October 2017

Confidential

Slide 23

Technical feasibility

Production volume of 2 beamlines similar to HFR

Electron beam

Two beamlines can produce

200.000 6d-Ci/year End of Processing

• Compare to HFR capacity of

170.000 6d-Ci /year End of Processing

Simulation results by NRG and RuG• Central 20 mm of disks :

762.612 Ci/yr End of Exposure @ 130 Ci/gr

Outer part of 30 mm of disks:

170.169 Ci/yr End of Exposure @ 37 Ci/gr

• Two beamlines of 30 mA at 60 MeV

• Ratio of activity between “End of Exposure”

and “6days End of Processing” is <7.5

• Mo-100 target of 30x30x56 mm3 with 50%

filling produced by 3D-printing

30 October 2017

Confidential

Slide 24

Mo-100 target 3D printed

100 micron features

Developed by

Developed by

Developed by

Isotope beamline

Transport lineProcess cell

Sample

chamber

Helium pumps

30 October 2017

Confidential

Slide 25

Isotope line

68m

16m

3,5m

Developed by

Picture generated by Rob Lansbergen

30 October 2017

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Slide 26

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Slide 27

LightHouseIsotopes