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European Journal of Nuclear Medicine and Molecular Imaging

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21.12.2021 | Original Article

⁸⁹Zr-labeled PSMA ligands for pharmacokinetic PET imaging and dosimetry of PSMA-617 and PSMA-I&T: a preclinical evaluation and first in man

verfasst von: Bastiaan M. Privé, Yvonne H. W. Derks, Florian Rosar, Gerben M. Franssen, Steffie M. B. Peters, Fadi Khreish, Mark Bartholomä, Stephan Maus, Martin Gotthardt, Peter Laverman, Mark W. Konijnenberg, Samer Ezziddin, James Nagarajah, Sandra Heskamp

Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging | Ausgabe 6/2022

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Abstract

Rationale

Prolonged in vivo evaluation of PSMA tracers could improve tumor imaging and patient selection for ¹⁷⁷Lu-PSMA-617 and ¹⁷⁷Lu-PSMA-I&T. In this study, we present the radiolabeling method of PSMA-617 and PSMA-I&T with the long-lived positron emitter ⁸⁹Zr to enable PET imaging up to 7 days post-injection. We compared the biodistribution of ⁸⁹Zr-PSMA-617 and ⁸⁹Zr-PSMA-I&T to those of ¹⁷⁷Lu-PSMA-617 and ¹⁷⁷Lu-PSMA-I&T, respectively, in a PSMA⁺ xenograft model. Moreover, we provide the first human ⁸⁹Zr-PSMA-617 images.

Materials and methods

PSMA ligands were labeled with 50-55 MBq [⁸⁹Zr]ZrCl₄ using a two-step labeling protocol. For biodistribution, BALB/c nude mice bearing PSMA⁺ and PSMA⁻ xenografts received 0.6 µg (0.6–1 MBq) of ⁸⁹Zr-PSMA-617, ⁸⁹Zr-PSMA-I&T, ¹⁷⁷Lu-PSMA-617, or ¹⁷⁷Lu-PSMA-I&T intravenously. Ex vivo biodistribution and PET/SPECT imaging were performed up to 168 h post-injection. Dosimetry was performed from the biodistribution data. The patient received 90.5 MBq ⁸⁹Zr-PSMA-617 followed by PET/CT imaging.

Results

⁸⁹Zr-labeled PSMA ligands showed a comparable ex vivo biodistribution to its respective ¹⁷⁷Lu-labeled counterparts with high tumor accumulation in the PSMA⁺ xenografts. However, using a dose estimation model for ¹⁷⁷Lu, absorbed radiation dose in bone and kidneys differed among the ¹⁷⁷Lu-PSMA and ⁸⁹Zr-PSMA tracers. ⁸⁹Zr-PSMA-617 PET in the first human patient showed high contrast of PSMA expressing tissues up to 48 h post-injection.

Conclusion

PSMA-617 and PSMA-I&T were successfully labeled with ⁸⁹Zr and demonstrated high uptake in PSMA⁺ xenografts, which enabled PET up to 168 h post-injection. The biodistribution of ⁸⁹Zr-PSMA-I&T and ⁸⁹Zr-PSMA-617 resembled that of ¹⁷⁷Lu-PSMA-I&T and ¹⁷⁷Lu-PSMA-617, respectively. The first patient ⁸⁹Zr-PSMA-617 PET images were of high quality warranting further clinical investigation.

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Titel: 89Zr-labeled PSMA ligands for pharmacokinetic PET imaging and dosimetry of PSMA-617 and PSMA-I&T: a preclinical evaluation and first in man
verfasst von: Bastiaan M. Privé
Yvonne H. W. Derks
Florian Rosar
Gerben M. Franssen
Steffie M. B. Peters
Fadi Khreish
Mark Bartholomä
Stephan Maus
Martin Gotthardt
Peter Laverman
Mark W. Konijnenberg
Samer Ezziddin
James Nagarajah
Sandra Heskamp
Publikationsdatum: 21.12.2021
Verlag: Springer Berlin Heidelberg
Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging / Ausgabe 6/2022
Print ISSN: 1619-7070
Elektronische ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-021-05661-0

Springer Medizin

Abstract

Rationale

Materials and methods

Results

Conclusion

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