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Cyclotron production of 68Ga and "in house" preparation of positron emission tomography (PET) radiopharmaceuticals

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Abstract

Solid targets and a medical cyclotron were used for the large-scale preparation of 68Ga. The target preparation, proton irradiation of a 68Zn-enriched target, dissolution of the target, separation of 68Ga from zinc, and labelling procedure for the [68Ga]Ga-DOTATOC, [68Ga]Ga-DOTANOC, and [68Ga]Ga-PSMA-11 radiopharmaceutical are presented. The radiopharmaceuticals were prepared with a good manufacturing practices quality of up to 6 GBq of the final product per batch at the end of synthesis (EOS) time. A quality control of 68Ga-labelled tracers showed an acceptable radiochemical purity and stable product at least five hours after the EOS. A separation procedure for the effective separation of 68Ga from an iron interferent was developed.

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References

  1. Rösch F (2013) 68Ge/68Ga Generators: past, present, and future. In: Baum RP and Rösch F (eds), Theranostics, Gallium-68, and other radionuclides, recent results in cancer research (194). Springer-Verlag Berlin Heidelberg

  2. The GalliaPharm® 68Ge/68Ga Radionuclide Generator https://static1.squarespace.com/static/564ee38be4b001fdb8d57bb5/t/5ac767286d2a7394c95706ca/1523017514896/7132-0025.pdf

  3. Galli Eo, a 68Ge/68Ga generator https://www.ire.eu/medias/354/Galli-Eo.pdf

  4. Alves F, Alves VHP, Do Carmo SJC, Neves ACB, Silva M, Abrunhosa AJ (2017) Production of copper-64 and gallium-68 with a medical cyclotron using liquid targets. Mod Phys Lett A 32(17):1740013. https://doi.org/10.1142/s0217732317400132

    Article  CAS  Google Scholar 

  5. Pandey MK, Byrne JF, Schlasner KN, Schmit NR, DeGrado TR (2019) Cyclotron production of 68Ga in a liquid target: effects of solution composition and irradiation parameters. Nucl Med Biol 74–75:49–55. https://doi.org/10.1016/j.nucmedbio.2019.03.002

    Article  CAS  PubMed  Google Scholar 

  6. Szelecsenyi F, Steyn GF, Kovács Z (2005) New cross-section data for the 66Zn(p, n)66Ga, 68Zn(p,3n)66Ga, natZn(p, x)66Ga, 68Zn(p,2n)67Ga and natZn(p, x)67Ga nuclear reactions up to 100 MeV. Nucl Instr and Meth B 234(4):375–386

    Article  CAS  Google Scholar 

  7. Raghad SM (2017) Evaluating cross-sections of gallium isotopes production using proton and deuteron Irradiation. Al-Mustansiriyah J Sci 28(2):184–187. https://doi.org/10.23851/mjs.v28i2.516

    Article  Google Scholar 

  8. European Patent Application EP 3 101 660 A1 (2016) Process for producing Gallium-68 through the irradiation of a solution target

  9. Thisgaard H, Kumlin J, Langkjær N, Chua J, Hook B, Jensen M, Kassaian A, Zeisler S, Borjian S, Cross M, Schaffer P, Hygum Dam J (2021) Multi-curie production of gallium-68 on a biomedical cyclotron and automated radiolabelling of PSMA-11 and DOTATATE. EJNMMI Radiopharm Chem. https://doi.org/10.1186/s41181-020-00114-9

    Article  PubMed  PubMed Central  Google Scholar 

  10. Alnahwi AH, Tremblay S, Ait-Mohand S, Beaudoin JF, Guérin B (2020) Automated radiosynthesis of 68Ga for large-scale routine production using 68Zn pressed target. App Radiat Isot 156:109014. https://doi.org/10.1016/j.apradiso.2019.109014

    Article  CAS  Google Scholar 

  11. Lin M, Paolillo V, Ta TR, Damasco J, Rojo RD, Carl JC, Melancon MP, Ravizzini GC, Le DB, Santos EB (2020) Fully automated preparation of [68Ga]Ga-PSMA-11 at curie level quantity using cyclotron-produced 68Ga for clinical applications. Appl Radiat Isot 155:108938. https://doi.org/10.1016/j.apradiso.2019.108936

    Article  CAS  Google Scholar 

  12. Lin M, Waligorski GJ, Lepera González C (2018) Production of curie quantities of 68Ga with a medical cyclotron via the 68Zn(p, n)68Ga reaction. Appl Radiat Isot 133:1–3. https://doi.org/10.1016/j.apradiso.2017.12.010

    Article  CAS  PubMed  Google Scholar 

  13. Tieu W, Hollis CA, Kuan KKW, Takhar P, Stuckings M, Spooner N, Malinconico M (2019) Rapid and automated production of [68Ga]gallium chloride and [68Ga] Ga-DOTA-TATE on a medical cyclotron Nucl. Med Biol 74–75:12–18

    Google Scholar 

  14. European Pharmacopoeia (2021) 10.3 Gallium (68Ga) Chloride (Accelerator—produced) Solution for Radiolabelling

  15. Hennrich U, Benešová M (2020) 68Ga-DOTA-TOC: the first FDA-approved 68Ga-radiopharmaceutical for PET Imaging. Pharm J 13(3):38. https://doi.org/10.3390/ph13030038

    Article  CAS  Google Scholar 

  16. Metrohm, Application Bulletin 317/2 e Determination of iron in the μg/L-range by polarography, Voltammetric determination for Fe concentrations < 200 μg/L, pp 3–5

  17. Moldovan Z, Neagu EA (2002) Spectrophotometric determination of trace iron(III) in natural water after its preconcentration with a chelating resin. J Serb Chem Soc 67:669–676

    Article  CAS  Google Scholar 

  18. Ilbert M, Bonnefoy V (2013) Insight into the evolution of the iron oxidation pathways. Biochim Biophys Acta Bioenerg 1827:161–175

    Article  CAS  Google Scholar 

  19. Metrohm, Application Bulletin 231/3 e, Determination of zinc, cadmium, lead, copper, thallium, nickel, and cobalt in water samples by anodic and adsorptive stripping voltammetry according to DIN 38406–16, Determination of Zn, Cd, Pb and Cu, pp 1–3

  20. Jussing E, Milton S, Samén E, Moein MM, Bylund L, Axelsson R, Siikanen J, Tran TA (2021) Clinically applicable cyclotron-produced gallium-68 gives high-yield radiolabeling of DOTA-based tracers. Biomolecules 11:1118. https://doi.org/10.3390/biom11081118

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Chung Y, Lee CW (2013) Electrochemistry of gallium. J Electrochem Sci Technol 4:1–18

    Article  CAS  Google Scholar 

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Acknowledgements

The authors gratefully acknowledge the International Atomic Energy Agency (IAEA) project F22073 ‘Production of the cyclotron-based galium-68 radioisotope and related radiopharmaceuticals’ for support for partial funding.

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Authors and Affiliations

  1. BIONT a.s, Karloveská 63, 824 29, Bratislava, Slovakia

    Simona Brisudová, Pavol Rajec, Marek Leporis, Ondrej Szöllös, Miloslav Štefečka, Rastislav Ondrejkovič, Miroslav Taranda, Zoltán Krascsenits & Zoltán Kassai

  2. Department of Nuclear Chemistry, Comenius University, Ilkovičová 6, 842 15, Bratislava, Slovakia

    Simona Brisudová, Pavol Rajec & Zoltán Krascsenits

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  1. Simona Brisudová
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  2. Pavol Rajec
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  5. Miloslav Štefečka
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Correspondence to Simona Brisudová.

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Brisudová, S., Rajec, P., Leporis, M. et al. Cyclotron production of 68Ga and "in house" preparation of positron emission tomography (PET) radiopharmaceuticals. J Radioanal Nucl Chem 332, 1419–1426 (2023). https://doi.org/10.1007/s10967-022-08732-0

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  • DOI: https://doi.org/10.1007/s10967-022-08732-0

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