World status on reactor and cyclotron radioisotope production

Transcription

1 World status on reactor and cyclotron radioisotope production Richard Zimmermann Chrysalium Consulting Mechelen, May 11, 2017

2 Global trends 2017 Second wave of growth with 177 Lu-Lutathera 2014 The therapeutic radiopharmaceuticals market takes off with Xofigo, boosting the global nuclear medicine market 2022 Third wave of growth with new radiotherapeutics Source: MEDraysintell (2016) 2

3 Global trends Global market The global market is expected to reach US$ 24 billion by 2030 Annual average growth of 11%. Diagnostic market to grow by 6% a year mainly driven by volume Therapeutic RP market to grow by 26% a year Major trends Split between diagnosis companies and therapeutic companies Increasing interest from conventional pharmaceutical companies (only therapy) RP companies are transforming in CMOs 3

4 Principe of Molecular Targeting Pathology Receptor Ligand / Vector Radio-isotopes Diagnostic 99m Tc, 18 F, 68 Ga Therapeutic 131 I, 177 Lu Linker + chelator 4

5 Different types of radioactivity Alpha (α): 2 protons + 2 neutrons: Therapy 7400x weight of electron Gamma: (γ-ray) SPECT imaging Beta minus: e - = high energy electron: Therapy Auger electron: e - = low energy electron: Therapy Beta plus: positron = antielectron (e + ) e - + e + -> 2γ : PET imaging 5

6 What you can see, you can treat Breast Cancer Lymphoma 6

7 7

8 Personalized medicine Selection of positive responders for a specific therapy Outcome prognosis and follow up of therapy Concept of Theranostics 8

9 Development of New RPs is Limited by Access to RNs Pharmaceutical grade Generators: 99 Mo/ 99m Tc, 68 Ge/ 68 Ga, ( 82 Sr/ 82 Rb) SPECT: ( 123 I), ( 111 In), 67 Ga, 201 Tl, 186 Re, 169 Er PET: 18 F, ( 124 I) Therapy: 131 I, 90 Y, 177 Lu, 153 Sm, 89 Sr, 223 Ra GMP grade Generators: - SPECT: - PET: 89 Zr Therapy: ( 166 Ho) Local availability Generators: ( 188 W/ 188 Re) SPECT: - PET: ( 15 O, 13 N, 11 C, 64 Cu) Therapy: ( 117m Sn) () brackets: locally available or expensive; blue color: difficult chemistry or limited applications - - By W/ 188 Re - ( 64 Cu) 212 Pb, ( 227 Th) ( 211 At, 225 Ac) 9

10 Development of New RPs is Limited by Access to RNs Pharmaceutical grade Generators: 99 Mo/ 99m Tc, 68 Ge/ 68 Ga SPECT: ( 123 I), 67 Ga, PET: 18 F, ( 124 I) Therapy: 131 I, 90 Y, 177 Lu GMP grade Generators: - SPECT: - PET: 89 Zr Therapy: ( 166 Ho) Local availability Generators: - SPECT: - PET: ( 15 O, 13 N, 11 C) Therapy: ( 117m Sn) () brackets: locally available or expensive; blue color: difficult chemistry or limited applications By W/ 188 Re 89 Zr 225 Ac, 211 At 188 W/ 188 Re - ( 64 Cu) 212 Pb, ( 227 Th) ( 211 At, 225 Ac) 10

11 Radionuclide manufacturing tools Reactor Tool to generate the bulk radionuclide or precursor e.g. 177 Lu, 99 Mo, 131 I Cyclotron Tool to generate bulk short-lived radionuclides e.g. 18 F, 111 In, 123 I, 67 Ga, 201 Tl Generator Tool to generate on-site very short lived radionuclides e. g. 99m Tc, 188 Re, 82 Rb, 68 Ga 11

12 Radiopharmaceuticals manufacturing tools Synthesis automates: The radionuclide is transformed in radiopharmaceutical Hot cells Tool containing the automates clean room Class C or B Final product: showing syringe protection and lead containers 12

13 Reactors 13

14 Reactor produced radionuclide Equipment PET SPECT Therapy Reactors Nuclear waste purification 51 Cr, 59 Fe, 75 Se, 99 Mo, ( 117m Sn), 125 I, 133 Xe, 32 P, 57 Co, 58 Co, 60 Co, 67 Cu, 89 Sr, 90 Sr, 105 Rh, ( 117m Sn), 131 I, 149 Pm, 153 Sm, 166 Ho, 169 Er, 177 Lu, 186 Re, 188 W, 199 Au, 223 Ra, 225 Ac, 227 Th 212 Bi, 212 Pb, 224 Ra, 225 Ac, 227 Th 14

15 Which tool for which radionuclide? Equipment PET SPECT Therapy Reactors 51 Cr, 59 Fe, 99 Mo, 125 I, 133 Xe, 32 P, 57 Co, 58 Co, 60 Co, 89 Sr, 90 Sr, 131 I, 153 Sm, 166 Ho, 169 Er, 177 Lu, 186 Re, 188 W, 223 Ra, Nuclear waste purification 212 Bi, 212 Pb, 224 Ra, 227 Th Major reactor medical products: 99 Mo, 131 I, 177 Lu 99m Tc represents 80% of diagnostic procedures 15

16 Total capacity expressed in 6-day kci/year Coqui, Alachua, FL, USA (259) HFR Petten, Netherlands (187 -> 242) 2000 BR2 Mol, Belgium (180 ->211) 2026 NRU Chalk River, Canada (187) - prolonged to March 2018 SHINE, Janesville WI, USA (24), > (192) 2021 NorthStar/MURR, USA upgrade (156) Horowitz (154) 1500 OPAL, Lucas Heigths, Australia (150) SAFARI, Pelindaba, South Africa (131) NorthStar, Beloit WI, USA (120) RA-10, Ezeiza, Argentina (120) MARIA, Swierck, Poland (95) 2030 KAERI, Busan, South Korea (86) Horowitz, Cadarache, F (75) LVR-15, Rez, Czech Republic (72) Niowave, USA (10 -> 70) FRM-II, Garching, Germany (67) -> 2054 RIAR Dimitrovgrad, Russia upgrade (67) RIAR 2 - RBMK (67) CARR, Fangshou, PR China (50) 500 OPAL (75) RMB, Ipeiro, Brazil (41) NorthStar/MURR, USA (39) RIAR, Russia (33) RA-3, Ezeiza, Argentina (18) Karpov, Obninsk, Russia (17) Running, or approved/under extension Approved and financed project/under construction Project still to be approved/financed Figures between brackets are maximum capacity per site (based on OECD July 2016 report, MEDraysintell 2016 report and companies' information) Blue line: Estimated needs 16

17 99 Mo/ 99m Tc By 2018 the 99 Mo shortage issue will be solved By 2022 there will be excess of capacity in 99 Mo Price of generators may even drop due to competition There will be a new shortage issue by , when Petten and Mol reactors will have to close (if not replaced by Pallas/Myrrha) As a consequence of the limited interest in SPECT in the past 10 years there is a very low number of new 99m Tc tracers available But 99m Tc will remain the cheapest radionuclide and SPECT the cheapest NM diagnostic modality 17

18 Cyclotrons 18

19 Cyclotrons 10 MeV 18MeV 30MeV 70MeV 19

20 Which tool for which radionuclide? Equipment PET SPECT Therapy Cyclotron <15 MeV (S - small size) 11 C, 13 N, 115 O, 8 F, 22 Na, 43 Sc, 64 Cu, 77 Br, 94m Tc, ( 124 I) ( 67 Ga), ( 111 In), 127 Xe [ 57 Co] d Cyclotron MeV (M - medium size) Cyclotron MeV (L - large size) [ 18 F] d, 44 Sc, 61 Cu, 63 Zn, [ 64 Cu] d, 68 Ga, 76 Br, 86 Y, [ 86 Y] He, 89 Zr, [ 89 Zr] d, 124 I 62 Zn, [ 64 Cu] d, 68 Ge, 72 Se, [ 76 Br] He, [ 82 Sr] He, [ 82 Sr] α, [ 86 Y] d 81 Rb, [ 81 Rb] He, [ 81 Rb] α, 99m Tc, ( 123 I) 44 Ti, 67 Ga, ( 99 Mo), ([ 99 Mo] α ), 111 In, ([ 111 In] α ), 123 I, ( 127 Xe), 201 Tl ( 57 Co), 103 Pd, 114m In, [ 125 I] d, 225 Ac ([ 32 P] d ), 47 Sc, ( 57 Co), ( 67 Cu), [ 117m Sn] α, ( 131 Cs), 169 Yb, 211 At Cyclotron MeV (X - extra-large size) ( 22 Na), 82 Sr ( 127 Xe) 67 Cu, ( 103 Pd), 117m Sn, 20

21 Which tool for which radionuclide? Equipment PET SPECT Therapy Cyclotron <15 MeV (S - small size) Cyclotron MeV (M - medium size) Cyclotron MeV (L - large size) Cyclotron MeV (X - extra-large size) 11 C, 13 N, 115 O, 18 F, 64 Cu 127 Xe 68 Ga, 89 Zr 99m Tc 103 Pd, 225 Ac 68 Ge 67 Ga, 111 In, 123 I, 201 Tl 47 Sc, 211 At 82 Sr 67 Cu, 117m Sn, 21

22 Worldwide Equipment - Summary Cameras [estimations 2016] and cyclotrons [real 2015 (*)] USA EU (geogr. w/o Russia) World (2016) World (est. 2025) SPECT 12,500 4,400 24,300 29,000 PET 2, ,600 8,600 Cyclotrons (*) (<25MeV) ,106 1,350 (*) Source: MEDraysintell (2016) Trends SPECT: slow evolution in Asia and replacement market PET cameras: faster growth but due to filling gaps Cyclotrons: 50 new units a year (Asia mainly) - saturation of sites Additional issues Limited access to shielded rooms 22

23 Economic considerations Value of the PET network ( 18 F - half-life 2 hours) France or Germany: hypothesis 5 centers - 5M in average: 25 M Extrapolation to Europe x 450/70 = 160M North American market: approx same size => World > 400M 124 I or 89 Zr: about 7M /site but only 2-4 required worldwide: 15-25M Exception short half life ( 123 I): >10 sites worldwide = >> 150M Reactor: investment of 500M- > 1,000M, but Extension of an existing SPECT or therapy site (e.g. 177 Lu) Estimated 3-5M /site (2-4 required worldwide): 10-20M Some exceptions e.g. 225 Ac probably > 100M 23 23

24 Linear accelerators 24

25 Summary: manufacturing capacity and needs SPECT 99 Mo/ 99m Tc: solved until I: PET missing infrastructure, but no new tracers 18 F: potential issue after Ga: 89 Zr: Therapy 177 Lu: 131 I: Alphatherapy 211 At: 225 Ac: need of sources of 68 Ge, of 68 Ge/ 68 Ga generators and 68 Ga available, need of slight extension solved solved need of a network Reactor Cyclotron need of an infrastructure, partially under construction 25 25

26 Thanks for your attention MEDraysintell 26