CERNMEDICIS Production disotopes selon lapproche ISOLDE pour la

CERN-MEDICIS: Production d’isotopes selon l’approche « ISOLDE » pour la recherche médicale Thierry Stora Isolde Users Workshop 18 th December 2012 T. Stora - Isolde Users Workshop

Overview But will be used to produce Innovative isotopes for this: When a CERN proton beam intercepts a target: (courtesy J. Lettry) Which can well lead to this result if not careful… 9/30/2020 T. Stora - Isolde Users Workshop 2

The ISOLDE facility The On-Line Isotope Mass Separator ISOLDE is a facility dedicated to the production of a large variety of radioactive ion beams for a great number of different experiments, e. g. in the field of nuclear and atomic physics, solid-state physics, life sciences and material science BT Y l ine Up to 50% of total CERN proton are delivered to ISOLDE TSR ? ? ? Experiment Hall Cryo for REX Class A work sector (courtesy M. Kowalska) (in 2011) 9/30/2020 T. Stora - Isolde Users Workshop 3

Multi-users capabilities GLM, GHM Dm/m = 15% But also… HRS GPS … 90% of 1. 4 Ge. V proton reach the beam dump past the Isolde production target 9/30/2020 T. Stora - Isolde Users Workshop (R. Luis) 4

Curie therapy Treatment of Lupus disease: Dr. Danlos, insitut Curie, 1 st proposed in 1901 By Pierre Curie Application of a source of Radium (223, 224? ) to skin lesions 9/30/2020 T. Stora - Isolde Users Workshop 5

Alpharadin® • Went through phase III clinical trials ( typically 1 development takes 10 years, 1 over 10000 molecules/formulations succeeds) • Should get approval from FDA next year (available through early Access Clinical Trial) • Marketed by Bayer Schering /Algeta • Is a « sophisticated » 223 Ra formulation (Ra. Cl 2) by intravenous injection. • Is applied for prostate/breast cancer treatment with bone metastasis 9/30/2020 T. Stora - Isolde Users Workshop 6

Estimated production from a Hg spallation target at EURISOL ~ 1/1000 will be produced At (HIE)-ISOLDE, But production can be optimised 109 particle/s collection for 1 hr is 1 m. Ci (4 e 7 Bq) for T 1/2=24 hr 1 m. Ci 28 Mg in 2 hrs with Ti foils 9/30/2020 T. Stora - Isolde Users Workshop 7

Other isotopes for PET imaging A production site in St-Genis Pouilly, France Spin-off from S. Buono, formerly at CERN 9/30/2020 T. Stora - Isolde Users Workshop 8

Should CERN-Medicis address conventional isotopes? (my personnal view) • No ! • Because of : – CERN mandate/mission – Technical characteristics of MEDICIS – Historical background – ISOLDE known for its cutting-edge R&D activities 9/30/2020 T. Stora - Isolde Users Workshop 9

ISOLDE activities 9/30/2020 10 -15 years ago Isolde users workshop, Dec 2011 & Following report ! T. Stora - Isolde Users Workshop 10

Test experiment Hello, My name is… Bombina bombina Prostate Cancer cells 152 Tb From ISOLDE • Peptide analog that specifically binds to prostate cancer tissues • Batch collected at ISOLDE and exported to CHUV • Tests on mice already showed better biodistribution (less toxicity to healthy tissues) than same peptide + 68 Ga Candidate for next therapeutic trials with 149 Tb/161 Tb (A. Gottberg, K. Johnston, RP, GS) 9/30/2020 T. Stora - Isolde Users Workshop 11

1000+ isotopes (for 70+ elements) “online” Exotic isotopes down to t 1/2 ~ 10 ms) Intensities up to 1011 ions/s 30+ types of targets Transfer lines 10+ ion sources 9/30/2020 T. Stora - Isolde Users Workshop 12

The « ISOL » filter In-target production rate A=152 A=83 Beam production rate (release + ionization) Mass separation 9/30/2020 T. Stora - Isolde Users Workshop 13

Full MEDICIS principle Activation of samples and batch separation fully transparent to Isolde operation Building : CERN Private fundation CERN KT fund 9/30/2020 Further fund requests In-kind LISOL T. Stora - Isolde Users Workshop 14

Example : 61 Cu Activity [Bq] (15 min decay) Isotope inventory Y 2 O 3 target (2 g/cm 3) 2 m. A proton beam 4 hours A=61 Cu 9/30/2020 T. Stora - Isolde Users Workshop Activity [Bq] (3 hours decay) 15 15

Adaptation of targets 5 cm diameter 9/30/2020 T. Stora - Isolde Users Workshop 16

Layout Transport system Target & Mass separator Medicis Spectroscopy & shipping Laboratory Buffer area 9/30/2020 T. Stora - Isolde Users Workshop 17

Layout update See posters, Report by R. Catherall 9/30/2020 T. Stora - Isolde Users Workshop 18

External partners Dr. Forni (Clin. Carouge) Prof. Morel, Prof. Buehler, Prof. Y. Seimbille, Prof. Ratib (HCUGE) Prof. D. Hanahan (ISREC, EPFL, Lausanne) Prof. F. Buchegger, Prof. J. Prior (CHUV, Lausanne) Prof M. Huyse, prof. P. van Duppen (Univ. Leuven) Prof. S. Lahiri (SINP, Kolkata) T. Stora - Isolde Users Workshop

External partners Prof D. Hanahan, Swiss Inst. For Exper. Cancer Research 9/30/2020 T. Stora - Isolde Users Workshop 20

MEDICIS Timeline • • Design of layout and building ongoing Civil engineering foreseen to start in 2013 (LS 1) MEDICIS Laboratory commissioning - mid 2015 Aim at starting production and shipping of first batches - end 2015 9/30/2020 T. Stora - Isolde Users Workshop 21

Project’s team @CERN: S. Marzari (Building), R. Catherall (HIE coord), T. Giles (Iso sep), R. Augusto (Fluka), Z. Lawson (Biological&KTT aspects), A. Polato (CV), E. Perez-Duenas (CE), K. Kershaw (HE), M. Stachura (Bio R&D), J. Vollaire (RP), A. Dorsival (RP), A. P. Bernardes (g-al safety), tbcont’d Thank you ! 9/30/2020 T. Stora - Isolde Users Workshop 22