MEDICAL RADIOISOTOPE PRODUCTION IN RESEARCH REACTORS

Transcription

1 MEDICAL RADIOISOTOPE PRODUCTION IN RESEARCH REACTORS BR2 Potential High-Flux Consequences Reactorfrom Ceased Production of Medical Radioisotope at the NRU Reactor Bernard PONSARD Radioisotopes Project Manager Chairman AIPES R&I WG BR2 Reactor 5 th Symposium on Medical Radioisotopes Production and Transportation Challenges 5 TH SYMPOSIUM ON MEDICAL RADIOISOTOPES MOL (BELGIUM) MAY 1/34 Mol, 05/05/2015

2 Medical Radioisotope Production in Research Reactors 1. Introduction 2. Production of radioisotopes for diagnostic 3. Production of radioisotopes for therapy 4. Challenges for the BR2 reactor 5. Conclusions Mo-99/Tc-99m BR2 Reactor 5 TH SYMPOSIUM ON MEDICAL RADIOISOTOPES MOL (BELGIUM) MAY /34

3 1. Introduction Research reactors are playing a key role in the production of radioisotopes for various applications in nuclear medicine, i.e. diagnostic (Tc-99m, ), therapy (I-131, Xe-133, Lu-177, Ir-192, Y-90, P-32, Ho-166, Ra-223, ) and palliation of metastatic bone pain (Sm-153, Re-186, Re-188, Sr-89, Sn-117m ). However, while the number of accelerators mainly cyclotrons for the production of medical radioisotopes is increasing, the supply of reactor-produced medical radioisotopes relies on a limited number of research reactors. This is especially the case for the production of Mo-99, avery crucial radioisotope as it decays into Tc-99m which is used in 80% of diagnostic nuclear imaging procedures carried out worldwide annually, i.e. 30 million examinations yearly. 5 TH SYMPOSIUM ON MEDICAL RADIOISOTOPES MOL (BELGIUM) MAY /34

4 High-Flux Reactors 1. Introduction SM3 (Dimitrovgrad; Russia); thermal neutron flux (E n < 0.5 ev) up to n/cm².s HFIR (Oak Ridge; USA); thermal neutron flux (E n < 0.5 ev) up to n/cm².s BR2 (Mol; Belgium); thermal neutron flux (E n < 0.5 ev) up to n/cm².s Medium-Flux Reactors MURR (Columbia; USA); thermal neutron flux (E n < 0.5 ev) up to n/cm².s HANARO (Daejeon; South Korea); thermal neutron flux (E n < 0.5 ev) up to n/cm².s HFR (Petten; NL); thermal neutron flux (E n < 0.5 ev) up to n/cm².s Low-Flux Reactors Thermal neutron flux (E n < 0.5 ev) below n/cm².s 5 TH SYMPOSIUM ON MEDICAL RADIOISOTOPES MOL (BELGIUM) MAY /34

5 1. Introduction Reactors Countries First criticality MW Φ th [e+14 n/cm².s] Days / year 1. Introduction SM-3 Russia ? HFIR United States BR2 Belgium NRU Canada MURR United States MARIA Poland HANARO Rep Korea HFR Netherlands SAFARI South Africa OPAL Australia OSIRIS France LVR-15 Czech Rep FRM-II Germany TH SYMPOSIUM ON MEDICAL RADIOISOTOPES MOL (BELGIUM) MAY /34

6 1. Introduction Current research reactors are ageing, expensive to replace and - due to safety and financial issues - a continuing source of public and political debate as it is currently the case in: France (no bridge between shutdown OSIRIS and start JHR reactor) Belgium (replacement of the BR2 reactor by MYRRHA) The Netherlands (replacement of the HFR reactor by PALLAS) Canada (definitive shutdown of the NRU reactor end of March 2018) The availability of research reactors with appropriate neutron fluxes and significant operating time is an important issues to ensure a reliable supply of medical radioisotopes in future. The current situation is a major concern in the Mo-99/Tc-99m supply chain, especially after the decisions taken recently to shut down definitively the OSIRIS reactor (France) in December 2015 and to cease routine Mo-99 production at the NRU reactor (Canada) from November 2016 (backup until 31 th of March 2018). 5 TH SYMPOSIUM ON MEDICAL RADIOISOTOPES MOL (BELGIUM) MAY /34

7 2. Production of radioisotopes for diagnostic : Mo-99/Tc-99m The worldwide supply of Mo-99 relies on a limited number of research 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% of diagnostic nuclear imaging procedures. These applications represent approximately 30 million examinations yearly worldwide. Mo-99/Tc-99m Generator Therefore, a weekly Mo-99 production of about 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 daughter Tc-99m (6 hours), a regular supply of 99 Mo/ 99m Tc generators to hospitals or central radiopharmacies is required. 5 TH SYMPOSIUM ON MEDICAL RADIOISOTOPES MOL (BELGIUM) MAY /34

8 2. Production of radioisotopes for diagnostic : Mo-99/Tc-99m The supply chain consists of : uranium target manufacturers nuclear reactors for target irradiation processing facilities to dissolve the irradiated targets and extract Mo-99 Mo-99/Tc-99m generators manufacturers radiopharmacies to elute Tc-99m from the generators and prepare radiopharmaceutical doses to be injected to the patients for diagnosis transport companies to ship the produced activities to the different participants involved in the supply chain. From the producers to the users No time to lose Nuclear Reactors Processing Facilities Hospitals Carriers More carriers Users 5 TH SYMPOSIUM ON MEDICAL RADIOISOTOPES MOL (BELGIUM) MAY /34

9 2. Production of radioisotopes for diagnostic : Mo-99/Tc-99m BR2 Reactor Targets shipment Targets manufacture Targets irradiation Mo-99/Tc-99m Targets processing 5 TH SYMPOSIUM ON MEDICAL RADIOISOTOPES MOL (BELGIUM) MAY /34

10 g 2. Production of radioisotopes for diagnostic : Mo-99/Tc-99m OPERATIONS INVOLVED IRRADIATION IN THE REACTOR UNLOADING FROM THE REACTOR Targets irradiation LOADING CONTAINERS SHIPMENT CONTAINERS PROCESSING IRRADIATED TARGETS SHIPMENT BULK Mo-99 MANUFACTURE and DELIVERY GENERATORS USE IN HOSPITALS TIME SCALE 150 HOURS 12 HOURS 4 HOURS 4 HOURS 12 HOURS 12 HOURS 12 HOURS 120 HOURS EVOLUTION OF THE MO-99 ACTIVITY 1000 Ci Mo-99 EOI / target 810 Ci / target 640 Ci bulk Mo Ci Mo Ci Mo-99 6-DAY Production of Mo-99/Tc-99m in the BR2 Reactor 5 TH SYMPOSIUM ON MEDICAL RADIOISOTOPES MOL (BELGIUM) MAY /34

11 g 2. Production of radioisotopes for diagnostic : Mo-99/Tc-99m The 6-day Ci is a unit of measure that takes the Mo-99 decay rate into account, the losses during shipments and processing, and represents an average amount of Mo-99 that would be available for use 6 days after processing Targets irradiation Mo-99 Global Demand About Ci Mo-99 6-day calibrated per week!!! Or about Ci Mo-99 6-days calibrated per year!!! Ci EOI Ci Mo-99 available for shipping Ci Mo-99 6-days 5 TH SYMPOSIUM ON MEDICAL RADIOISOTOPES MOL (BELGIUM) MAY /34

12 AIPES = Association of Imaging Producers & Equipment Suppliers 2. Production of radioisotopes for diagnostic : Mo-99/Tc-99m Ten reactors are currently represented in the AIPES Reactors and Isotopes Working Group: NRU (Canada), BR2 (Belgium), HFR (The Netherlands), OSIRIS (France), SAFARI (South Africa), MARIA (Poland), LVR-15 (Czech Republic), OPAL (Australia), RA-3 (Argentina) and FRM-II (Germany; currently not irradiating targets for Mo-99; start 2018). The estimated Mo-99 production capacities of the current irradiators are: 2014 OECD 5 TH SYMPOSIUM ON MEDICAL RADIOISOTOPES MOL (BELGIUM) MAY /34

13 AIPES = Association of Imaging Producers & Equipment Suppliers 2. Production of radioisotopes for diagnostic : Mo-99/Tc-99m NRU MDS NORDION MALLINCKRODT LANTHEUS GE HEALTHCARE BR2 IRE IBA CIS BIO HFR OSIRIS MALLINCKRODT MALLINCKRODT MARIA LVR-15 REACTOR PROCESSING MO-99 MANUFACTURE GENERATORS RA-3 NTP SAFARI CNEA NTP CNEA OPAL ANSTO ANSTO Mo-99 Global Supply Chain 5 TH SYMPOSIUM ON MEDICAL RADIOISOTOPES MOL (BELGIUM) MAY /34

14 HFR Reactor SAFARI Reactor RA-3 Reactor AIPES = Association of Imaging Producers & Equipment Suppliers 2. Production of radioisotopes for diagnostic : Mo-99/Tc-99m OPAL Reactor NRU Reactor LVR-15 Reactor OSIRIS Reactor BR2 Reactor FRM-II Reactor MARIA Reactor 5 TH SYMPOSIUM ON MEDICAL RADIOISOTOPES MOL (BELGIUM) MAY /34

15 AIPES = Association of Imaging Producers & Equipment Suppliers 2. Production of radioisotopes for diagnostic : Mo-99/Tc-99m Six processors are currently represented in the AIPES R&I Working Group: AECL/NORDION (Canada), ANSTO (Australia), IRE (Belgium), MALLINCKRODT (The Netherlands), NTP (South Africa) and CNEA (Argentina). The estimated Mo-99 production capacities of the current processors are: 2014 OECD To ensure security of supply, the AIPES R&I WG tries : to achieve the best possible coordination of the reactor operating periods to provide an optimal global coverage during planned reactor shutdown periods for refueling and maintenance to solve problems through its Emergency Response Team (ERT) 5 TH SYMPOSIUM ON MEDICAL RADIOISOTOPES MOL (BELGIUM) MAY /34

16 AIPES = Association of Imaging Producers & Equipment Suppliers 2. Production of radioisotopes for diagnostic : Mo-99/Tc-99m 5 TH SYMPOSIUM ON MEDICAL RADIOISOTOPES MOL (BELGIUM) MAY /34

17 AIPES = Association of Imaging Producers & Equipment Suppliers 2. Production of radioisotopes for diagnostic : Mo-99/Tc-99m To follow the maximum global irradiation capacity for Mo-99 production week by week the AIPES Reactors and Isotopes Working Group developed the "VERSAILLES Mo-99 MODEL" which has been validated according to data provided by the OECD/NEA (2013/2014) reports and feedback delivered by the AIPES representatives (processors and generators manufacturers) for 2013 and This model is a suitable tool to assist scheduling the reactor operating periods with respect to an optimal Mo-99 production. The model is able to identify periods at risk which need to be further investigated at processor and generator manufacturer level. A reactor production capacity below the '6-d' Ci red line during a particular week does not mean that the reduced Mo-99 production capacity would result into a severe Mo-99 shortage which would not be manageable. 5 TH SYMPOSIUM ON MEDICAL RADIOISOTOPES MOL (BELGIUM) MAY /34

18 AIPES = Association of Imaging Producers & Equipment Suppliers 2. Production of radioisotopes for diagnostic : Mo-99/Tc-99m Results of the AIPES "VERSAILLES Mo-99 MODEL" applied to the year 2015 during BR2's scheduled extended shutdown: 5 TH SYMPOSIUM ON MEDICAL RADIOISOTOPES MOL (BELGIUM) MAY /34

19 2. Production of radioisotopes for diagnostic : Mo-99/Tc-99m Alternative methods for producing Mo-99 and Tc-99m without the use of HEU Reactor Production Routes Fission of solid LEU targets : 235 U(n,fission) 99 Mo Fission of LEU in solution : 235 U(n,fission) 99 Mo Neutron capture : 98 Mo(n,γ) 99 Mo Accelerator Production Routes Photofission reaction : 238 U(γ,fission) 99 Mo Photonuclear reaction : 100 Mo(γ,n) 99 Mo Photoneutrons generated from e - beam for fission LEU in solution D-T neutron generators to fission LEU in solution: 235 U(n,fission) 99 Mo Spallation neutron source production (ADS) : 235 U(n,fission) 99 Mo Direct Tc-99m production by cyclotron : 100 Mo(p,2n) 99m Tc 5 TH SYMPOSIUM ON MEDICAL RADIOISOTOPES MOL (BELGIUM) MAY /34

20 3. Production of radioisotopes for therapy : Lu-177, W-188/Re-188, Research reactors are not only producing Mo-99. They are also routinely producing Ir-192 (T1/2=74.2 d) for curietherapy and several radioisotopes for metastatic bone pain palliation as Re-186 (T1/2=3.8 d), Sm-153 (T1/2=46.7 h), Y-90 (T1/2=64 h), Sr-89 (T1/2=50.5 d),... The very attractive Lu-177 (T1/2=6.7 d) for targeted therapy of small tumours (prostate, ) and metastatic bone pain palliation can be produced by both direct and indirect routes in research reactors: Direct route: 176 Lu (n th, γ) 177 Lu; yield = 30 Ci/mg at EOI Indirect route: 176 Yb (n th, γ) 177 Yb 177 Lu; yield = 0.07 Ci/mg 176 Yb at EOI 5 TH SYMPOSIUM ON MEDICAL RADIOISOTOPES MOL (BELGIUM) MAY /34

21 Reactor Production of Lu Production of radioisotopes for therapy : Lu-177, W-188/Re-188, Direct Route 98.5% enriched Lu-176 Yb-176 n, γ σ = 2090 barn Indirect Route by Beta Decay n, γ σ = 2.85 barn Lu days Yb hours Lu-177m 160 days 5 TH SYMPOSIUM ON MEDICAL RADIOISOTOPES MOL (BELGIUM) MAY /34 β - + Carrier-Free route Improved/optimized separation required

22 Reactor Production of W-188/Re Production of radioisotopes for therapy : Lu-177, W-188/Re-188, Double Neutron Capture 186 W 97.8% enriched n, γ 37.9 b 187 W n, γ σ = 64 b β Decay 188 W 69.7 days "Burn-Up" n, γ σ = 12 b 189 W 187 Re n, γ σ = 76.4 b Direct Route β Decay 188 Re 188 Os (Stable) 17.0 hours β max 2.12 MeV γ 155 kev (15%) 5 TH SYMPOSIUM ON MEDICAL RADIOISOTOPES MOL (BELGIUM) MAY /34

23 Reactor Production of W-188/Re Production of radioisotopes for therapy : Lu-177, W-188/Re-188, 5 TH SYMPOSIUM ON MEDICAL RADIOISOTOPES MOL (BELGIUM) MAY /34

24 4. Challenges for the BR2 reactor Reactor type High Flux Materials Testing Reactor Pressurized, light water Be matrix, compact core HEU fuel (93% 235 U) LEU conversion project in place In operation since 1963 Refurbishment : & Currently: February June 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 100 MW Height : 0.91 m 5 TH SYMPOSIUM ON MEDICAL RADIOISOTOPES MOL (BELGIUM) MAY /34

25 4. Challenges for the BR2 reactor The Belgian Nuclear Research Centre which operates the BR2 High-Flux Reactor made a strategical decision to maintain an important multipurpose neutron source on site. The BR2 reactor is considered as a major facility worldwide for the routine supply of Mo-99/Tc-99m, I-131, Xe-133, Lu-177, Ir-192, Re-186, Sm-153, Er-169, Y-90, P-32, Sr-89, Sn-117m, W-188/Re-188, I-125, and for the development of new medical radioisotopes as Ac-227/Ra-223,... The BR2 reactor is currently in temporary shutdown for a scheduled period of 16 months from February 2015 until June 2016 to replace its beryllium matrix mainly. The refurbishment will allow a safe and reliable operation of the reactor for another period of at least 10 years with an upgraded annual operating regime of up to 8 cycles, i.e.up to operating days per year, subject to the economics. 5 TH SYMPOSIUM ON MEDICAL RADIOISOTOPES MOL (BELGIUM) MAY /34

26 4. Challenges for the BR2 reactor This major maintenance intends to make the bridge with the projected replacement facility MYRRHA (Accelerator Driven System, ADS) scheduled to start in 2025, subject to fundings. MYRRHA ADS 5 TH SYMPOSIUM ON MEDICAL RADIOISOTOPES MOL (BELGIUM) MAY /34

27 4. Challenges for the BR2 reactor The main challenges for the BR2 reactor are: to perform its refurbishment according to the established planning to perform its first cycle 01/2016A in July 2016 to upgrade its operating regime up to 8 cycles per year to strengthen its position on the global Mo-99 market maintain its irradiation capacity: Ci 6d per week increase its irradiation capacity: Ci >>> Ci 6d per year i.e. 30% >>> 40% of the current global annual Mo-99 demand to convert from HEU into LEU targets for Mo-99 production limit the loss of irradiation capacity by suitable irradiation devices irradiation of LEU targets have been performed before refurbishment successfull results for both IRE and MALLINCKRODT to develop the production of new medical radioisotopes 5 TH SYMPOSIUM ON MEDICAL RADIOISOTOPES MOL (BELGIUM) MAY /34

28 4. Challenges for the BR2 reactor Several LEU targets have been successfully irradiated in 2014 for both IRE and MALLINCKRODT before the scheduled shutdown of the BR2 reactor for refurbishment. PIE (Post Irradiation Examinations) on several irradiated LEU targets are currently performed in s Hot Labs. 5 TH SYMPOSIUM ON MEDICAL RADIOISOTOPES MOL (BELGIUM) MAY /34

29 BR2 s refurbishment is on track : Removal of the BR2 reactor cover on 24/04/ Challenges for the BR2 reactor 5 TH SYMPOSIUM ON MEDICAL RADIOISOTOPES MOL (BELGIUM) MAY /34

30 BR2 s refurbishment is on track : Removal of the BR2 reactor cover on 24/04/ Challenges for the BR2 reactor 5 TH SYMPOSIUM ON MEDICAL RADIOISOTOPES MOL (BELGIUM) MAY /34

31 BR2 s refurbishment is on track : 1 st Beryllium channel removed on 01/05/ Challenges for the BR2 reactor Be channel G300 5 TH SYMPOSIUM ON MEDICAL RADIOISOTOPES MOL (BELGIUM) MAY /34

32 5. Conclusions The definitive shutdown of the OSIRIS (France) reactor at the end of 2015 and the decision taken by the Government of Canada to cease routine Mo-99 production at the NRU (Canada) reactor from November 1, 2016 will result in a reduction of about 30% of the current global Mo-99 production capacity by the end of 2016, i.e. a challenge for the BR2 reactor to strengthen its position on the global Mo-99 market. The Mo-99 production by irradiation of LEU targets in research reactors will remain the main production route in future. Main challenges for research reactors regarding the production of medical radioisotopes in the period : Safe and reliable operation Security of supply of medical radioisotopes Successful conversion of High Enriched Uranium (HEU) into Low Enriched Uranium (LEU) targets for Mo-99/Tc-99m production Development of new medical radioisotopes for therapy, especially for Targeted Alpha Therapy (TAT) and Personalized Medicine (PM), i.e. providing "the right patient with the right the right the right time" Complementarity with accelerators for medical radioisotope production Timely decision for replacement projects (MYRRHA, PALLAS, ) to ensure continuity of production in the supply chain 5 TH SYMPOSIUM ON MEDICAL RADIOISOTOPES MOL (BELGIUM) MAY /34

33 Thank You For Your Attention 5 TH SYMPOSIUM ON MEDICAL RADIOISOTOPES MOL (BELGIUM) MAY /34

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