Automated production of Cu-64, Zr-89, Ga-68, Ti-45, I-123 and I-124 with a medical cyclotron, using a commercial solid target system
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Presented at Terachem 2018 in Vienna by Comecer's R&D Specialist Mario Malinconico. More ALCEO resources here: https://www.comecer.com/updated-guide-to-alceo-resources/
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Automated production of Cu-64, Zr-89, Ga-68, Ti-45, I-123 and I-124 with a medical cyclotron, using a commercial solid target system
- 1. Automated production of Cu-64, Zr-89, Ga-68, Ti-45, I-123 and I-124 with a medical cyclotron, using a commercial solid target system Mario Malinconico Comecer R&D Specialist
- 3. Improved Modularity 3 “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
- 6. 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)
- 7. Cooling system 7 • 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
- 8. Shuttles 8 Shuttle dimensions : D28x35mm Alceo Halogen I-123/124 target shuttle (Haynes alloy + Pt) Hi-tmp melting shuttle Alceo Metal Zr-89/Ti-45 target shuttle (Aluminium + Pt) Foil shuttle Alceo Metal Cu-64/Ga-68 target shuttle (Aluminium + Pt) Plating shuttle
- 9. EDS 3.0 9 Main features • Storage targets • Sending/receiving the target to/from PTS • Ni-64 plating • Cu-64 Dissolution • Zn-68 plating • Ga-68 Dissolution • Zr-89 Dissolution • Ti-45 Dissolution PTS TADDEO-PRF Dissolutionirradiatedtaregt
- 10. 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 10 • EDS or • DISSOLUTION UNIT Labeling Cu-64 Production kit Ti-45/Zr-89 Production kit Ga-68 Production kit
- 12. Cu-64 PRODUCTION 12 Ni powder NiNO3 solution 64Ni 64Cu 64Ni(p,n)64Cu 9ml Copper Chloride in HCl 0,5M (new cartridge final volume 1,5mL) Expectd yield 1,5mCi/uAh (max current 40uA) • Electroplate • Clean after plating • Send • Irradiate • Receive • Cu-Dissolve&Cu-Purify • Ni recovery • Clean after purification • Waste cassette 15h
- 13. HOT TEST Cu-64 13 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) 2.5mCiuAh PAPER BURN 10uA 15sec 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
- 14. HOT TEST Cu-64 14 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/uAh
- 15. ICPMS 15 mg plating Fe (ppb) Co (ppb) Ni (ppb) 46,2 8510 4.3 17180 48,6 7300 3.8 22420 47,1 3560 6 10950
- 16. LABELING 16 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
- 18. Zr-89 PRODUCTION 34 • 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)
- 19. HOT TEST Zr-89 19 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
- 20. 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 HOT TEST Zr-89
- 21. GAMMA 37
- 23. Ga-68 Production 23 Znpowder 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
- 24. Hot Test Ga-68 24 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)
- 25. Performances 25 GALLIUM (Ga-68) 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.
- 26. 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
- 28. Ti-45 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)
- 29. Hot Test Ti-45 29 PAPER BURN 10uA 15sec BEAM Current 25uA Irradiation 2 h 89ZrProduction Activity 75,7mCi Yield (EOB) 8,43mCi/uA
- 30. Hot Test Ti-45 30 45Ti 45Ti 45Ti 45Ti 89Zr
- 33. I-123/124 Production 33 • 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-123/124 Iodine Te(p,n)I TeO2 powder + alumina • Melt 0,8ml NaI in NaOH 1M Expected yield 0,1 mCi/uAh (max current 10uA) for 124I / 0,4 mCi/uAh (max current 10uA) for 123I
- 34. Mixing of TeO2+Al2O3 Insertion of the mixed powders inside the shuttle Heating ramp (final step ~900 °C) Cooling down Inside EVP 123/124I PRODUCTION DEPOSIT 44
- 35. 35 Loss of weight: <2mg
- 37. Performances 37 EXPECTED YIELDS Isotope Max Current [µA] Typical Irradiation Time [h] Yield EOB [mCi/µAh] Cu-64 40 6 ≥1,5 Zr-89 20 3 ≥0,35 I-124 10 6 ≥0,1 I-123 10 6 ≥0,4 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