Journal of Radiopharmaceuticals and Molecular Probes (대한방사성의약품학회지)

Korean Society of Radiopharmaceuticals and Molecular Probes (대한방사성의약품학회)
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Study on the Solution for the Reduced [68Ga]Ga-PSMA-11 Synthesis Yield

  • Sang Min Shin (Innovation Center for Molecular Probe Development, Department of Nuclear Medicine, Chonnam National University Hwasun Hospital) ;
  • Young Si Park (Innovation Center for Molecular Probe Development, Department of Nuclear Medicine, Chonnam National University Hwasun Hospital) ;
  • Ji Hoon Kang (Innovation Center for Molecular Probe Development, Department of Nuclear Medicine, Chonnam National University Hwasun Hospital) ;
  • Hea Ji Kim (Innovation Center for Molecular Probe Development, Department of Nuclear Medicine, Chonnam National University Hwasun Hospital) ;
  • Hwa Youn Jang (Innovation Center for Molecular Probe Development, Department of Nuclear Medicine, Chonnam National University Hwasun Hospital) ;
  • Jeongmin Son (Department of Nuclear Medicine, Severance Hospital, Yonsei University College of Medicine) ;
  • Jun Young Park (Department of Nuclear Medicine, Severance Hospital, Yonsei University College of Medicine)
  • Received : 2024.02.22
  • Accepted : 2024.03.18
  • Published : 2024.06.30
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Abstract

[68Ga]Ga-PSMA-11 is a prostate-specific membrane antigen (PSMA)-targeting radiopharmaceutical based on lysine-urea-glutamic acid derivatives. This study aimed to identify the cause of the irregular decrease in the radiosynthesis yield of [68Ga]Ga-PSMA-11 and to suggest a solution. An irregular decrease in production yield occurred during the synthesis of [68Ga]Ga-PSMA-11 using a cassette-based automatic synthesizer. Although the reagents used in synthesizing [68Ga]Ga-PSMA-11 were replaced with new products, the irregular decrease in radiosynthesis yield continued. In addition, cassettes, equipment, and operating programs used in the cassette-based automatic synthesizer operated normally. On the other hand, when eluting with 0.6 N hydrochloric acid(HCl), leakage was found at the outlet line connection site of the 68Ge/68Ga generator. The 68Ge/68Ga generator was eluted with 0.6 N HCl two to four hours before synthesis to remove impurities and improve the synthetic yield reduction. No further irregular yield reduction occurred after using this method. In the event of an irregular decrease in the radiolabeling yield, the pretreatment method developed in this study would help produce [68Ga]Ga-PSMA-11 injections with a stable labeling yield.

Keywords

References

  1. Choi Kim WT, Kim WJ. Current update in basic research in Korea: prostate cancer. Korean J Urol Oncol 2013;11(2):63-70.
  2. Yoo KH, Lee HL. Early prostate cancer in old-aged patients. Korean J Urol Oncol 2010;8(3):97-101.
  3. Kang MJ, Won YJ, Lee JJ, Jung KW, Kim HJ, Kong HJ, Im JS, Seo HG. Cancer statistics in Korea: incidence, mortality, survival, and prevalence in 2019. Cancer Res Treat 2022;54:330-44.
  4. Ha YS, Kim KT, Nam W, Park HZ, Yoo S, Lee CH, Chung HS, Choi WS, Kim J, Shin J, Kim JH, Kwak C. A survey on the quality of life of prostate cancer patients in Korean prostate cancer patients association. Korean J Urol Oncol 2022;20(4):265-72.
  5. Ghafoor S, Burger IA, Vargas AH. Multimodality imaging of prostate cancer. J Nucl Med 2019;60(10):1350-8.
  6. Hong JH. An update of prostate-specific membrane antigen theranostics in prostate cancer. Korean J Urol Oncol 2022;20(4): 207-22.
  7. Padhani AR, Lecouvet FE, Tunariu N, Koh DM, De Keyzer F, Collins DJ, Sala E, Fanti S, Vargas HA, Petralia G, Schlemmer HP, Tombal B, Bono J. Rationale for Modernising Imaging in Advanced Prostate Cancer. Eur Urol Focus 2017;3(2-3):223-39.
  8. Capasso G, Stefanucci A, Tolomeo A. A systematic review on the current status of PSMA-targeted imaging and radioligand therapy. Eur J Med Chem 2024;263:115966.
  9. Horoszewicz JS, Kawinski E, Murphy GP. Monoclonal antibodies to a new antigenic marker in epithelial prostatic cells and serum of prostatic cancer patients. Anticancer Res 1987;7:927-35.
  10. Adnan A, Basu S. PSMA Receptor-based PET-CT: The basics and current status in clinical and research applications. Diagnostics (Basel) 2023;13(1):158.
  11. Kahn D, Williams RD, Seldin DW, Libertino JA, Hirschhorn M, Dreicer R, Weiner GJ, Bushnell D, Gulfo J. Radioimmunoscintigraphy with 111Indium labeled CYT-356 for the detection of occult prostate cancer recurrence. J Urol 1994;152:1490-5.
  12. Liu H, Moy P, Kim S, Xia Y, Rajasekaran A, Navarro V, Knudsen B, Bander NH. Monoclonal antibodies to the extracellular domain of prostate-specific membrane antigen also react with tumor vascular endothelium. Cancer Res 1997;57:3629-34.
  13. Tateishi U. Prostate-specific membrane antigen (PSMA)-ligand positron emission tomography and radioligand therapy (RLT) of prostate cancer. Jpn J Clin Oncol 2020;50(4):349-56.
  14. Barrio M, Fendler WP, Czernin J, Herrmann K. Prostate specific membrane antigen (PSMA) ligands for diagnosis and therapy of prostate cancer. Expert Rev Mol Diagn 2016;16(11):1177-88.
  15. Kumar K, Mathur A. Total chemical synthesis of PSMA-11: API for 68Ga-PSMA-11 used for prostate cancer diagnosis. Eur J Med Chem 2021;3:100014.
  16. Gleason GI. A positron cow. Int J Appl Radiat Isot 1960;8:90-4.
  17. Loc'h C, Maziere B, Comar D. A new generator for ionic gallium-68. J Nucl Med 1980;21(2):171-3.
  18. Shetty D, Lee YS, Jeong JM. 68Ga-labeled radiopharmaceuticals for positron emission tomography. Nucl Med Mol Imaging 2010;44:233-40.
  19. Hennrich U, Benesova M. [68Ga]Ga-DOTA-TOC: The first FDA-Approved 68Ga-radiopharmaceutical for PET imaging. Pharmaceuticals (Basel) 2020;13(3):38.
  20. Hennrich U, Eder M. [68Ga]Ga-PSMA-11: The first FDAapproved 68Ga-radiopharmaceutical for PET imaging of prostate cancer. Pharmaceuticals (Basel) 2021;14(8):713.
  21. Park JY, Son JM, Kang WJ. Development of an automated synthesizer for the routine production of Ga-68 radiopharmaceuticals. Korean J Clin Lab Sci 2023;55(4):253-60.
  22. Hofman MS, Lawrentschuk N, Francis RJ, Tang C, Vela I, Thomas P, Rutherford N, Martin JM, Frydenberg M, Shakher R, Wong LM, Taubman K, Ting Lee S, Hsiao E, Roach P, Nottage M, Kirkwood I, Hayne D, Link E, Marusic P, Matera A, Herschtal A, Iravani A, Hicks RJ, Williams S, Murphy DG; proPSMA Study Group Collaborators. Prostate-specific membrane antigen PET-CT in patients with high-risk prostate cancer before curativeintent surgery or radiotherapy (proPSMA): a prospective, randomised, multicentre study. Lancet 2020;395:1208-16.
  23. Zhang X, Liu F, Payne AC, Nickels ML, Bellan LM, Manning HC. High-Yielding Radiosynthesis of [68Ga] Ga-PSMA-11 using a low-cost microfluidic device. Mol Imaging Biol 2020;22(5):1370-9.
  24. Wichmann CW, Ackermann U, Poniger S, Young K, Nguyen B, Chan G, Sachinidis J, Scott AM. Automated radiosynthesis of [68Ga]Ga-PSMA-11 and [177Lu]Lu-PSMA-617 on the iPHASE MultiSyn module for clinical applications. J Labelled Comp Radiopharm 2021;64(3):140-6.
  25. Lin M, Paolillo V, Ta RT, Damasco J, Rojo RD, Carl JC, Melancon MP, Ravizzini GC, Le DB, Santos EB. Fully automated preparation of 68Ga-PSMA-11 at curie level quantity using cyclotron-produced 68Ga for clinical applications. Appl Radiat Isot 2020;155:108936.
  26. Shahrokhi P, Masteri Farahani A, Tamaddondar M, Rezazadeh F. The utility of radiolabeled PSMA ligands for tumor imaging. Chem Biol Drug Des 2022;99(1):136-61.
  27. Kopka K, Benesova M, Barinka C, Haberkorn U, Babich J. Glu-Ureido-based inhibitors of prostate-specific membrane antigen: lessons learned during the development of a novel class of low-molecular-weight. Theranostic Radiotracers. J Nucl Med 2017;58(Suppl 2):17S-26S.
  28. Lawhn-Heath C, Salavati A, Behr SC, Rowe SP, Calais J, Fendler WP, Eiber M, Emmett L, Hofman MS, Hope TA. Prostate-specific membrane antigen PET in prostate cancer. Radiology 2021;299(2):248-60.
  29. Debnath S, Zhou N, McLaughlin M, Rice S, Pillai AK, Hao G, Sun X. PSMA-targeting imaging and theranostic agents-current status and future perspective. Int J Mol Sci 2022;23(3):1158.
  30. Sudbrock F, Fischer T, Zimmermanns B, Guliyev M, Dietlein M, Drzezga A, Schomacker K. Characterization of SnO2-based 68Ge/68Ga generators and 68Ga-DOTATATE preparations: radionuclide purity, radiochemical yield and long-term constancy. EJNMMI Res 2014;4(1):36.
  31. Roesch F. Maturat ion of a key resource - the germanium-68/gallium-68 generator: development and new insights. Curr Radiopharm 2012;5(3):202-11.
  32. Kim GG, Lee JY, Kim SW, Hur MG, Yang SD, Park JH. Study on synthesis of 68GeO2 and behavior of 68Ga3+ for generator column. J Radiat Ind 2016;10(4):189-92.
  33. Kumar K. The current status of the production and supply of gallium-68. Cancer Biother Radiopharm 2020;35(3):163-6.
  34. Oehlke E, Le VS, Lengkeek N, Pellegrini P, Jackson T, Greguric I, Weiner R. Influence of metal ions on the 68Ga-labeling of DOTATATE. Appl Radiat Isot 2013;82:232-8.
  35. Cusnir R, Cakebread A, Cooper MS, Young JD, Blower PJ, Ma MT. The effects of trace metal impurities on Ga-68-radiolabelling with a tris(3-hydroxy-1,6-dimethylpyridin-4-one) (THP) chelator. RSC Adv 2019;9(64):37214-21.