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Synthesis of radiometals from solid targets used for radiolabeling

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Synthesis of radiometals from solid targets used for radiolabeling

  1. 1. Synthesis of radiometals from solid targets used for radiolabeling Mario Malinconico, Comecer R&D Specialist
  2. 2. 2 ALCEO SOLID TARGET
  3. 3. GE PETTrace - Not shielded cyclotron GE PETTrace - Self shielded cyclotron Generic external beam line IBA Cyclone or Kiube cyclotron Target System - PTS • Installed in the cyclotron beam exit port • Receives the target shuttle from the modules with a complete automatic pneumatic transfer (pipe 35 mm)
  4. 4. PTS & Cooling system Cooling System 4 • Installed outside the bunker • Cools down the target under irradiation (He/water flows) • Supply description • Power • Compressed air • Helium cooling • Water cooling IN and OUT
  5. 5. Shuttles 5 Shuttle dimensions : D28x35mm Alceo Halogen 123/124I target shuttle (Haynes alloy + Pt) Alceo 64Cu Metal target shuttle (Aluminium + Pt) Alceo 68Ga Metal target shuttle (Aluminium + Pt) Alceo 89Zr Metal target shuttle (Aluminium + Pt) Hi-tmp melting shuttle Foil shuttle Plating shuttle Alceo 45Ti Metal target shuttle (Aluminium + Pt)
  6. 6. EDS 3.0 Main features 6 • storage targets • Sending/receiving the target to/from PTS • 64Ni plating • 64Cu Dissolution • 68Zn plating • 68Ga Dissolution • 89Zr Dissolution • 45Ti Dissolution PTS TADDEO-PRF Dissolutionirradiatedtaregt
  7. 7. EDS 3.0 Cross-contamination free and modular design 7 Ni Plating Cu dissolution Zr dissolution Zn Plating Ga dissolution Dedicated circuit for NiDedicated circuit for Zn Pick&Place Pick&Place
  8. 8. Taddeo-PRF • Dissolution • Cu: hot HCl 6M • Zr: HCl 6M drop-by-drop • Ga: hot HCl 10M • Purification • Cu: ion exchange resin with 6M HCl. • Ga: ion exchange resin with 1M HCl. • Zr: hydroxamate resin with 1M oxalic acid 8 • EDS or • DISSOLUTION UNIT Labeling 64Cu Production kit 45Ti/89Zr Production kit 68Ga Production kit
  9. 9. Improved Modularity 9 “Modularity” means: • a single target able to produce all the isotopes with an automatic transfer system • a single module able to produce different isotopes keeping safe the risks of cross- contamination • the possibility to switch between isotopes without complex setup and a quick chemical preparation 64Cu 89Zr 203Pb ALCEO METAL ALCEO HALOGEN 123/124I68Ga 45Ti 44Sc
  10. 10. 64Cu Production 10 Ni powder NiNO3 solution • Electroplate • Clean after plating • Send • Irradiate • Receive • Cu-Dissolve&Cu-Purify • Ni recovery • Clean after purification • Waste cassette 64Ni 64Cu 64Ni(p,n)64Cu 15h  9ml Copper Chloride in HCl 0,5M (new cartridge in the near future final volume 1,5mL)  Expectd yield 1,5mCi/uAh (max current 40uA)
  11. 11. Hot Test – 64Cu 11 PAPER BURN 10uA 15sec PLATING 44mg BEAM EOB 12:24 Current 30uA Irradiation 2,18h 64Cu Production Activity 146mCi Measure Time 15:22 Yield (EOB) 2.5mCiuA h PAPER BURN unknow PLATING 48,5mg BEAM EOB 12:40 Current 30uA Irradiation 1 h 64Cu Production Activity 61,4 Measure Time 14:40 Yield (EOB) 2,28mCi/uA *h
  12. 12. Hot Test – 64Cu 12 PAPER BURN 10uA 15sec PLATING 49mg BEAM EOB 16:00 Current 35uA Irradiation 6h 64Cu Production Activity 518 mCi Measure Time 18:00 Yield (EOB) 2.48mCi/u Ah
  13. 13. ICPMS 13 DATE mg plating Fe (ppb) Co (ppb) Ni (ppb) 10/JAN/2017 46,2 8510 4.3 17180 11/JAN/2017 48,6 7300 3.8 22420 12/JAN/2017 47,1 3560 6 10950
  14. 14. Labeling 14 Method: [64Cu]CuCl2 was added to H2-ATSM in DMSO and allowed to react over 5 min, then purified over C18 to give [64Cu]Cu-ATSM
  15. 15. 68Ga Production 15 Zn powder ZnCl2 solution • Electroplate • Clean after plating • Send • Irradiate • Receive • Ga-Dissolve&Ga-Purify • Zn recovery • Clean after purification • Waste cassette 68Zn 68Ga 68Zn(p,n)68Ga  5mL Gallium Chloride in HCl 1M  Expectd saturation yield 45mCi/uA (max current 35uA) 6h
  16. 16. Hot Test – 68GA 16 PAPER BURN PLATING 57,9mg BEAM Start Beam 10:00 EOB 10:19 Current 10uA Irradiation 180min 68Ga Production Activity EOB 399mCi Yield (EOB) 47,4 mCiuA PAPER BURN PLATING 49,1mg BEAM Start Beam 10:00 EOB 10:19 Current 10uA Irradiation 20min 68Ga Production Activity EOB 45,31 mCi 10:19 (9/9/16) Yield (EOB) 24,5mCiuA DEGRADER 320um (14,4MeV) DEGRADER 640um (12,1MeV)
  17. 17. Performances 17 GALLIUM (68Ga) CHLORIDE SOLUTION FOR RADIOLABELLING Gamma analysis comparison ALCEO- GENERATOR production European Pharmacopoeia • Half life: 62-74min Test Result Radionuclidic purity % 67Ga at EOP = 0,019% pH <2 Fe (ppb) Prod1: 332 Prod2: 1350 Zn (ppb) Prod1: 371 Prod2: 5130 GALLIUM (68Ga) CHLORIDE SOLUTION FOR RADIOLABELLING European Pharmacopoeia Gallium-68: min 99.9 %of the total radioactivity • pH = max 2. • Iron = maximum 10µg/GBq. • Zinc = maximum 10µg/GBq.
  18. 18. 18 68Ga-DOTATATE 68Ga-PSMA Products SYNTHESIS HPLC EOS activity (MBq) Synthesis yield Decay corrected yield Radiochemical purity Free 68Ga3+ DOTATATE 888 76,0% 88,6% 91,3% 0,25% PSMA 570 79,2% 89,6% 99,0% Not detected
  19. 19. 89Zr Production • Send • Irradiate • Receive • Zr-Dissolve • Zr-Purify • Clean after purification • Waste cassette 89Y 89Zr 89Y(p,n)89Zr Foil D15, 5mm thickness 0,25mm  1,3ml Zirconium Oxalate in Oxalic acid 1M  Expected yield 0,35mCi/uAh (max current 25uA)
  20. 20. Hot Test – 89Zr 20 PAPER BURN 8uA 12sec BEAM EOB 11:00 Current 23uA Irradiation 18min 89Zr Production Activity 3,59 Measure Time 13:00 Yield (EOB) 0,49 mCi/uA*h PAPER BURN 10uA 15sec BEAM EOB 12:00 Current 30uA Irradiation 3 h 89ZrProduction Activity 104,5mCi Measure Time 18:07 Yield (EOB) 1,17 mCi/uAh
  21. 21. 21 PAPER BURN 10uA 15sec BEAM EOB 12:24 Current 25uA Irradiation 30min 89Zr Production Activity 5,91mCi Measure Time 14:52 Yield (EOB) 0,48mCi/uA*h PAPER BURN 10uA 15sec BEAM EOB 10:30 Current 25uA Irradiation 30min 89Zr Production Activity 6,35mCi Measure Time 12:35 Yield (EOB) 0,51mCi/uA*h
  22. 22. Gamma
  23. 23. 23
  24. 24. 45Ti Production • Send • Irradiate • Receive • Ti-Dissolve • Ti-Purify • Clean after purification • Waste cassette 45Sc 45Ti 45Sc(p,n)45Ti Foil D15, 5mm, thickness 0,25mm  1,2ml Titanium Oxalate in Oxalic acid 1M  Expectd saturation yield 9mCi/uA (max current 25uA)
  25. 25. Hot Test – 45Ti 25 PAPER BURN 10uA 15sec BEAM EOB Current 25uA Irradiation 2 h 89ZrProduction Activity 75,7mCi Measure Time Yield (EOB) 8,43mCi/uA
  26. 26. Hot Test – 45Ti 26
  27. 27. Hot Test – 45Ti 27 45Ti 45Ti 45Ti 45Ti 89Zr
  28. 28. Alceo Halogen The EVP module performs the following operations automatically: • target shuttle transfer between hot cell and cyclotron • deposit of the isotope (Tellurium oxide melting) to be irradiated inside the target shuttle • iodine evaporation from the irradiated target • iodine recovery via basic solution The EVP is designed to eliminate problems related to the module decontamination and cross-contamination because it has been developed thanks to the “disposable cassette” technology. 28 PTS
  29. 29. 123/124I Production 29 • Send • Irradiate • Receive • Iodine Evaporation (heat to trap iodine on glass support coated with NaOH) • Iodine recovery (to release the iodine using a basic solution) Te Iodine Te(p,n) I TeO2 powder + alumina • Melt
  30. 30. Performances 30 EXPECTED YIELDS Isotope Max Current [µA] Typical Irradiation Time [h] Yield EOB [mCi/µAh] Result [mCi] Cu-64 40 6 ≥1,5 360 Zr-89 20 3 ≥0,35 20 I-124 10 6 ≥0,1 6 I-123 10 6 ≥0,4 24 EXPECTED YIELDS Isotope Max Current [µA] Typical Irradiation Time [h] Saturation Yield [mCi/µA] Ga-68 30 3 ≥45 Ti-45 25 3 ≥10 GALLIUM (68Ga) CHLORIDE Saturation Yield [mCi/µAh] ≥45 Irradiation time = 3h Applied current = 30µA Expected Activity > 1Ci 68Ga production of 1100 mCi

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