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The ISOLPHARM Project ISOL technique for radiopharmaceuticals development

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The ISOLPHARM Project ISOL technique for radiopharmaceuticals development

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  1. XIV Seminar on Software for Nuclear, Subnuclear and Applied Physics, Alghero, 8th June 2017 TheISOLPHARMProject ISOL technique for radiopharmaceuticals development Michele Ballan INFN –LNL michele.ballan@lnl.infn.it Michele Ballan

  2. Overview • ⚛The SPES projectat LNL • ⚛Radiopharmaceutical production: currenttechniques • ⚛ISOLPHARM: a new methodbased on ISOL technique • ⚛Innovative radio-isotopes for nuclear medicine (ISOLPHARM2) • ⚛Experimentalactivities • ⚛Conclusions Michele Ballan

  3. SPES Facility Layout • New infrastructure for: • Application Facility • Cyclotron • RIB facility Michele Ballan

  4. SPES: The future of LNL SPES is: 1) A second generation ISOL facility (for neutron-rich ion beams) 2) An interdisciplinary research center (for p,n applications) SPES-DRIVER SPES-RIB facility Financed & Under construction In commissioning Production & re-accelerationofexoticbeams, from p-inducedFissionon UCx • Cyclotroninstallation & commissioning: • E=70 MeVprotonbeam, I= 750 mA SPES for medicine SPES Neutronfacility Proposal Financed LARAMED & ISOLPHARM projects Radisotopes for medicalapplications Accelerator based neutron source (Proton and NeutronFacility for AppliedPhysics) Michele Ballan

  5. What is a radiopharmaceutical? Radiopharmaceuticals are medicines that deliver a predefined amount of radiation to a target tissue for diagnostic or therapeutic purposes depending on the mechanism of decay Nuclear medicine applications Therapeutic agents Diagnostic agents Radionuclidesproperties: Decayproperties Chemicalproperties Half-life Feasibility of large scale production Michele Ballan

  6. ISOL vs others Nuclear reactor Traditional methods • Low specific activity levels • High neutron fluxes required • Irradiation of targets of the same element • → Isotopic impurities (carrier added - radioisotopes) Cyclotron New method: • β- radionuclides can be easily produced as carrier-free isotopes • No nuclear reactor required Michele Ballan

  7. The Specificactivity The specific activity is a measure of the activity per mass and is usually expressed in units of GBq/mg or Ci/mg. A) Radioisotopes diluted by non therapeutic atoms of the same element have low specific activity. Carrier-added radionuclides B) Radioisotopes present only in the mass of the element of interest have high specific activity. Carrier-free radionuclides Michele Ballan

  8. ISOLPHARM Method overview The ISOLPHARM method is capable of selecting and isolating a SINGLE ISOTOPE → extremely high specific activity ISOL PHARM Michele Ballan

  9. The ISOLPHARMpatent The use of ISOL technique for the production of radiopharmaceuticals is a INFN PATENT Patent title: «Method for producing beta emitting radiopharmaceuticals and beta emitting radiopharmaceuticals thus obtained» EU patent CANADA patent US patent Michele Ballan

  10. ISOLPHARM (1st phase): produced radionuclides In target production of 89Sr and 90Y* using a standard UCx target Alreadydeveloped and tested! In target production of 64Cu using a Ni-based target Under development Michele Ballan

  11. Specificactivity (the case of 89Sr) Traditional production methods (reactor) New method Isotopiccontamination in the substrate Isobariccontamination in the substrate Difficult chemical separation Easy chemicalseparation High specificactivity Lowspecificactivity ~ 0,004 GBq/mg ~ 597 GBq/mg Michele Ballan

  12. Isotope production: UCX target PPB: 40 MeV, 200 μA b) a) [nuclide/s] b) a) Michele Ballan

  13. SPES UCXtarget yield: other isotopes? • A lot of ISOL beams can be potentially produced: • Only a few of the produced isotopes are currently used/studied in nuclear medicine (traditional techniques allow the production of a limited variety of radioisotopes) • Is it possible that other isotopes will be interesting as radiopharmaceuticals “active core”? Other ISOL isotopes? ISOLPHARM2 ISOLPHARM isotopes [nuclide/s] Michele Ballan

  14. Other ISOL Isotopes of medical interest? (light) Selectioncriteria • Diagnosis • Theragnostics • Therapy Michele Ballan

  15. Other ISOL Isotopes of medical interest? (heavy) Almost 60 ISOL isotopeswerefound! (up to now) • Diagnosis • Theragnostics • Therapy Michele Ballan

  16. Innovative Target concepts: overview • ISOL production of the desiredisotopesrequiresspecific targets. • Targets have to be: • Solid • Refractory(more refractorythan the element for whichtheyweredesigned) • Three target concepts are currently under investigation: • ⚛UCX target (Operation temperature: 2200°C) • ⚗ Target R&D and state of art: • ☢ Innovative isotopes production: 111Ag • ⚛ZrGe target (Operation temperature: 1800°C) • ⚗Target R&D and state of art: • ☢ Innovative isotopes production: As & Gaisotopes • ☢64/67Cu unexpected production! • ⚛TiC/TiB2target (Operation temperature: 2000°C) • ⚗Target R&D and state of art: • ☢Innovative isotopesproduction: Sc isotopes Nuclearreactionsstudied Designed Tested Nuclearreactionsstudied Designed Tested Nuclearreactionsstudied Designed Tested Michele Ballan

  17. 111Ag, 64-67Cu, 43-44-47Sc production (ISOLPHARM 2) 111Ag SPES UCx target PPB 40 MeV , 200 µA 64-67Cu SPES ZrGe target PPB 70 MeV , 100 µA Up to 40 mCi (67Cu) – 1500 mCi (64Cu) in target after 5 days! Up to 2 Ci in target after 5 days! 43-44-47Sc SPES TiC target PPB 40 MeV , 200 µA Up to 870 mCi (43Sc) – 6450 mCi (44Sc) – 2200 mCi (47Sc) in target after 5 days! Michele Ballan

  18. Activity done so far at LNL - UNIPD-DSF Beamdeposition @ LNL Simulation of the process using stable ion beams thanks to the SPES test bench (front-end off-line) Activities @ UNIPD-DSF Extraction from the substrate, quantification and chemical separation of the deposited element Ion beams produced, deposited, dissolved and analyzed: Sr+, Y+, I+, Cu+ (4 master, 2 PhD. students) Michele Ballan

  19. Conclusions: what’s next? • ⚛Cross check of the Fluka calculated yields using different models (Geant4) • ⚛ Performing of the first studies with radioactive ion beams (after 2019) • ⚛Building an ISOLPHARM national community: UNIPD (Industrial Engineering, Pharmaceutical Sciences, Physics & Chemistry Departments), INFN (INFN-PD, INFN-FE, INFN-NL, INFN-TIFPA) and hospitals (Castelfranco Veneto, Reggio Emilia) are involved. • ⚛ Building an ISOLPHARM international community: POLATOM (Poland) & NCSR-DEMOKRITOS (Greece) are involved in an European project. Some interest also from PSI & CERN ISOLDE – MEDICIS (Switzerland). Michele Ballan

  20. Thank you for your kind attention Michele Ballan

  21. & to the RIB production group… Michele Ballan