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Reply to: Byproducts in the synthesis of [68Ga]Ga-PSMA-11

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Data availability

Data associated with this work can be found within this reply, our original protocol2 and the associated Matters Arising from Makarem et al.3.

References

  1. Clore, J. & Scott, P. J. H. [68Ga]PSMA-11 for positron emission tomography (PET) imaging of prostate-specific membrane antigen (PSMA)-positive lesions in men with prostate cancer. Expert Rev. Mol. Diagn. 24, 565–582 (2024).

    Article  CAS  PubMed  Google Scholar 

  2. Rodnick, M. E. et al. Synthesis of 68Ga-radiopharmaceuticals using both generator-derived and cyclotron-produced 68Ga as exemplified by [68Ga]Ga-PSMA-11 for prostate cancer PET imaging. Nat. Protoc. 17, 980–1003 (2022).

  3. Makarem, A., Han, J. & Klika, K. D. Byproducts in the synthesis of [68Ga]Ga-PSMA-11. Nat. Protoc. https://doi.org/10.1038/s41596-025-01164-6 (2025).

  4. Eder, M. et al. 68Ga-complex lipophilicity and the targeting property of a urea-based PSMA inhibitor for PET imaging. Bioconjug. Chem. 23, 688–697 (2012).

    Article  CAS  PubMed  Google Scholar 

  5. Afshar-Oromieh, A. et al. PET imaging with a [68Ga]gallium-labelled PSMA ligand for the diagnosis of prostate cancer: biodistribution in humans and first evaluation of tumour lesions. Eur. J. Nucl. Med. Mol. Imaging 40, 486–495 (2013).

    Article  CAS  PubMed  Google Scholar 

  6. Carlucci, G. et al. 68Ga-PSMA-11 NDA approval: a novel and successful academic partnership. J. Nucl. Med. 62, 149–155 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Wang, I. E. et al. A comparison of routine [68Ga]Ga-PSMA-11 preparation using Locametz and Illuccix kits. EJNMMI Radiopharm. Chem. 9, 87 (2024).

    Article  PubMed  PubMed Central  Google Scholar 

  8. Eder, M. et al. Novel preclinical and radiopharmaceutical aspects of [68Ga]Ga-PSMA-HBED-CC: a new PET tracer for imaging of prostate cancer. Pharmaceuticals 7, 779–796 (2014).

  9. Vogg, A. et al. 68Ga-PSMA-11 prepared with the Telix kit versus a traditional synthesiser: does it matter? J. Nucl. Med. 62, 1463 (2021).

    Google Scholar 

  10. Assadi, M. & Dadgar, H. Quality control and GMP synthesis of 68Ga-prostate-specific membrane antigen-11 for detection of low- and high-grade prostate cancer. World J. Nucl. Med. 19, 93–98 (2019).

    PubMed  PubMed Central  Google Scholar 

  11. Abghari-Gerst, M. A comprehensive assessment of 68Ga-PSMA-11 PET in biochemically recurrent prostate cancer: results from a prospective multi-center study in 2005 patients. J. Nucl. Med. 63, 567–572 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Martin, S. et al. Identification, characterization, and suppression of side products formed during the synthesis of [177Lu]Lu-PSMA-617. J. Med. Chem. 64, 4960–4971 (2021).

    Article  CAS  PubMed  Google Scholar 

  13. Ioppolo, J. A., Alvarez de Eulate, E., Cullen, D. R., Mohamed, S. & Morandeau, L. Development of a high-performance liquid chromatography method for rapid radiochemical purity measurement of [18F]PSMA-1007, a PET radiopharmaceutical for detection of prostate cancer. J. Label Compd. Radiopharm. 66, 58–72 (2023).

  14. Cardinale, J. et al. Procedures for the GMP-compliant production and quality control of [18F]PSMA-1007: a next generation radiofluorinated tracer for the detection of prostate cancer. Pharmaceuticals 10, 77 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  15. Wang, Y. et al. Preparation of 68Ga-PSMA-11 with a synthesis module for micro PET-CT imaging of PSMA expression during prostate cancer progression. Contrast Media Mol. Imaging 2018, 8046541 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  16. Migliari, S. et al. Development and validation of a high-pressure liquid chromatography method for the determination of chemical purity and radiochemical purity of a [68Ga]-labeled Glu–urea–Lys(Ahx)-HBED-CC (positron emission tomography) tracer. ACS Omega 2, 7120–7126 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Fuscaldi, L. L. et al. Standardization of the [68Ga]Ga-PSMA-11 radiolabeling protocol in an automatic synthesis module: assessments for PET imaging of prostate cancer. Pharmaceuticals 14, 385 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

We thank A. Afshar-Oromieh, K. Kopka (now at HZDR) and their colleagues at the University Hospital of Heidelberg and the German Cancer Center (DKFZ) Heidelberg for the valuable assistance in qualifying UM for clinical production of [68Ga]Ga-PSMA-11 for the original protocol. P.J.H.S. thanks the University of Michigan Department of Radiology for financial support, as well as M. E. Rodnick for implementing the [68Ga]Ga-PSMA-11 syntheses used at UM and described in the original protocol.

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Authors

Contributions

K.G. and P.J.H.S. conceived and developed the original project and provided supervision and funding. D.S. and A.K. conducted radiosyntheses and QC at RPA. S.E. assisted with project development and target and cyclotron aspects at RPA. M.J.F. is a PET physician, provided funding for the RPA contribution and contributed to the manuscript. All authors contributed to this reply.

Corresponding authors

Correspondence to Katherine Gagnon, Stefan Eberl or Peter J. H. Scott.

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Competing interests

K.G. is an employee of GE HealthCare. The other authors declare no competing interests.

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Katsifis, A., Stark, D., Fulham, M.J. et al. Reply to: Byproducts in the synthesis of [68Ga]Ga-PSMA-11. Nat Protoc (2025). https://doi.org/10.1038/s41596-025-01163-7

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