new medical radioisotope production at br2 · 2018. 11. 21. · tb-152/tb-161, tb-155/tb-161, …)...

MEDICIS – Specialized Training on Radioisotope Production – MOL (Belgium) – SEPT 2017 1/22

PONSARD B. Copyright © 2017

SCK•CEN

Potential Consequences from Ceased Production of Medical Radioisotope at the NRU Reactor

Medical Radioisotope Production at BR2

MEDICIS - Promed Specialized Training on Radioisotope Production

Mol, 06/09/2017

Bernard PONSARDRadioisotopes Project Manager

Chairman AIPES R&I WGBR2 Reactor – [email protected]



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1. Introduction

2. The BR2 Reactor

3. Production of radioisotopes for diagnostic

4. Production of radioisotopes for therapy

5. Conclusions

BR2 Reactor

Perspectives for Radioisotope Production in the BR2 Reactor



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The BR2 high-flux reactor operatedby the Belgian Nuclear ResearchCentre (SCK•CEN) is not only one ofthe world's most powerful materialtesting reactors, it is also recognizedas a major facility for the globalproduction of radioisotopes.

The refurbishment performed recently(2015 – 2016) will ensure a safe andreliable reactor operation for anotherperiod of 10 years, at least.

The current operating regime based on6 cycles (147 operating days) per yearcould be upgraded up to 8 cycles (200operating days) subject to theeconomics.

1. Introduction



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1. Introduction



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The new Beryllium Matrix

1. Introduction



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The BR2 reactor is a major player in the production ofradioisotopes worldwide: High neutron fluxes (thermal up to e+15 n/cm².s and fast up to 6

e+14 n/cm².s), large irradiation volumes, very flexible, … but limitedby its operating regime (140 – 200 operating days per year).

100 MW

1. Introduction



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Reactor type High Flux Materials Testing Reactor Pressurized, light water Be matrix, compact core HEU fuel (93% 235U) LEU conversion project in place In operation since 1963 Refurbishments:

1979-1980 _1995-1997 _ 2015-2016 Aluminium pressure vessel

Geometry : hyperboloid of revolution Easy access to the top and bottom Diameter : 1 to 2 m Height : 8.6 m

Very compact core Diameter : 1.05 m Height : 0.91 m

100 MW

2. The BR2 Reactor



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Typical configuration

Unique shape

2. The BR2 Reactor



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From U-235

To Mo-99

Targets unloading

3. Production of radioisotopes for diagnostic : Mo-99/Tc-99m



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The worldwide supply of Mo-99 relies on a limited number ofresearch reactors and processing facilities.

Its production is essential for nuclear medicine as Tc-99m,obtained from Mo-99/Tc-99m generators, is used in about 80% ofdiagnostic nuclear imaging procedures.

These applications represent approximately 30 millionexaminations yearly worldwide.

Therefore, a weekly Mo-99 production of about 9.000 Ci '6-day'calibrated is required to supply North America (53%), Europe(23%), Asia (20%) and the rest of the world (4%).

Given the short half-lives of Mo-99 (66 hours) and its daughterTc-99m (6 hours), a regular supply of 99Mo/99mTc generators tohospitals or central radiopharmacies is required.

Mo-99/Tc-99m Generator




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Are currently represented in the AIPES Reactors &Isotopes Working Group (R&I WG) which has the task tosecure the global supply of Mo-99:

Eleven reactors : BR2 (Belgium), HFR (The Netherlands),SAFARI (South Africa), MARIA (Poland), LVR-15 (CzechRepublic), OPAL (Australia), RA-3 (Argentina), FRM-II(Germany; currently not irradiating targets for Mo-99; 2018),NRU (Canada; no routine production from November 2016),OSIRIS (France; shutdown) / JHR (France; under constructionto replace OSIRIS from 2022).

Six processors : IRE (Belgium), CURIUM MALLINCKRODTMedical B.V. (The Netherlands), ANSTO Health (Australia),NTP (South Africa), CNEA (Argentina) and CNL/NORDION(Canada; no routine production from November 2016).




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Mo-99/Tc-99m Generator




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Targets manufacture

Targets irradiation

Targets shipment

Mo-99/Tc-99m

BR2 Reactor

Targets processing

Hospital




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The BR2 reactor has the largest world's installed irradiationcapacity for Mo-99 production.

Reactors Countries Targets Operating weeks / year

Irradiation capacities / week

[6-day Ci ]

Irradiation capacities / year

[6-day Ci ]

End of operation

BR2 Belgium HEU 27 7 800 210 600 > 2026HFR The Netherlands HEU 39 6 200 241 800 2024

(NRU) (Canada) (HEU) (40) (4 680) (187 200) (Nov 2016)SAFARI South Africa HEU/LEU 44 3 000 130 700 2030LVR-15 Czech Republic HEU 30 3 000 90 000 2028MARIA Poland HEU 36 2 700 95 000 2030OPAL Australia LEU 43 2 150 92 450 2055RA-3 Argentina LEU 46 400 18 400 2027

With an installed irradiation capacity of 7.800 '6-day' Ci per week,the BR2 reactor is able to produce at least : 25% of the global Mo-99 demand in average 65% in peak periods

Ref: Nuclear Energy Agency, NEA/SEN/HLGMR (2017)2, April 2017, www.oecd-nea.org




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In addition to the current production of radioisotopes for therapy(I-131, Lu-177, Ir-192, Ho-166, Y-90, P-32, …) and for palliation ofmetastatic bone pain (Sm-153, Re-186, Re-188, Sr-89, Sn-117m,Ra-223, …), nuclear medicine is offering new perspectives.

Radioisotopes as Lu-177 are already largely used for targetedradionuclide therapy ( TRNT ) but others are under evaluation asmedium-energy β- emitters having diagnostic partners, high linearenergy transfer ( LET ) and Auger electron emitters ( Tb-161 ).


Isotopes Half-life T1/2

Decay mode

Average Energy β-

Average Energy γ

Lu-177 6,71 d β- 134 keV 208 keVSc-47 3,35 d β- 162 keV 159 keVCu-67 2,58 d β- 141 keV 186 keVTb-161 6,90 d β-, Auger e- 154 keV 75 keV



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The concept of personalized medicine based on 'theranostics'is increasingly seen as a promising approach in which singleradioisotopes or 'matched pairs' (Sc-44/Sc-47, Cu-64/Cu-67,Tb-152/Tb-161, Tb-155/Tb-161, …) are selected to enable pre-therapy imaging and dosimetry (PET or SPECT) followed bythe administration of an appropriate therapeutic dose (β- or α) tominimize the effect on healthy tissues.


Matched Pairs Half-life T1/2

Decay modeAverage Energy

β-

β+ orα / Average Energy γ

Ga-68 / Lu-177 0,05 d / 6,71 d β+ / β- 134 keV 890 keV / 208 keVSc-44 / Sc-47 3,97 h / 3,35 d β+ / β- 162 keV 632 keV / 159 keV

Cu-64 / Cu-67 0,53 d / 2,58 d β+ / β- 141 keV 278 keV / 186 keVTb-152 / Tb-161 17,5 h / 6,90 d β+ / β-,Auger e- 154 keV 1,08 MeV / 75 keVTb-155 / Tb-161 5,32 d / 6,90 d EC,γ/β-,Auger e- 154 keV 95 keV / 75 keVTb-149 / Tb-161 4,12 h / 6,90 d α / β-,Auger e- 154 keV 3,97 MeV / 75 keV



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Another challenge for research reactors as BR2 is to bequalified for the production of therapeutic Y-90 and Ho-166microspheres for the treatment of metastatic liver cancer.

Radioembolization refers to a therapy in which millions ofradioactive microspheres are injected into the hepatic arterycombining embolization – selective occlusion of bloodvessels by microspheres – with internal radiation therapy.

This procedure consists in the selective instillation ofradioactive microspheres using a catheter into the hepaticartery that feeds the tumor.

The microspheres block the supply of blood to the cancercells and deliver a high dose of radiation to the tumor whilesparing normal tissues.




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BTG TheraSphere® : Yttrium-90 / glass

QuiremSpheres® : Holmium-166 / PLLA

Radioembolization with Y-90 and Ho-166 microspheres

SIR-Spheres® : Yttrium-90 / resin



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Studies have found promizing results for the treatment ofmetastatic liver cancer by Y-90 and Ho-166 microspheres.


Isotopes Half-life T1/2

Decay mode

Average Energy β-

Average Energy γ

Y-90 64,2 h β- 0,94 MeV -Ho-166 26,8 h β- 1,84 MeV 81 keV

Y-90 and Ho-166 both emit highenergy beta particles for tumoreradication

Y-90 is a pure beta emitter Ho-166 also emits gamma

radiation which allows forquantitative nuclear imaging

Holmium is paramagnetic andtherefore visible on MRI

BTG TheraSphere® : Yttrium-90 / glass

SIR-Spheres® : Yttrium-90 / resin

QuiremSpheres® : Holmium-166 / PLLA

β- β-



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Thank You For Your Attention …

5. Conclusions The refurbishment of the BR2 reactor will ensure a safe

and reliable reactor operation for another period of 10 years,at least. The BR2 reactor recovered its position for the global

production of medical (and industrial) radioisotopes. This position could be reinforced in future by increasing the

operating regime from 6 to 8 cycles, subject to the economics. New perspectives have been identified for the development

of new therapeutic procedures in the field of personalizedmedicine ( “theranostics” ) and radioembolization.

And last but not least, special efforts are expected to bemade for “Targeted Alpha Therapy” (TAT).



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new medical radioisotope production at br2 · 2018. 11. 21. · tb-152/tb-161, tb-155/tb-161, …)...

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