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

Privé BM, Derks YH, Rosar F, Franssen GM, Peters SM, Khreish F, Bartholomä M, Maus S, Gotthardt M, Laverman P, Konijnenberg MW, Ezziddin S, Nagarajah J, Heskamp S (2022)

Publication Type: Journal article

Publication year: 2022

Journal

European Journal of Nuclear Medicine and Molecular Imaging Springer Verlag (Germany)

Book Volume: 49

Pages Range: 2064-2076

Journal Issue: 6

DOI: 10.1007/s00259-021-05661-0

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.

Involved external institutions

Universitätsklinikum des Saarlandes (UKS) DE Germany (DE) Radboud University Nijmegen Medical Centre / Radboudumc of voluit Radboud Universitair Medisch Centrum (UMC) NL Netherlands (NL)

How to cite

APA:

Privé, B.M., Derks, Y.H., Rosar, F., Franssen, G.M., Peters, S.M., Khreish, F.,... Heskamp, S. (2022). 89Zr-labeled PSMA ligands for pharmacokinetic PET imaging and dosimetry of PSMA-617 and PSMA-I&T: a preclinical evaluation and first in man. European Journal of Nuclear Medicine and Molecular Imaging, 49(6), 2064-2076. https://doi.org/10.1007/s00259-021-05661-0

MLA:

Privé, Bastiaan M., et al. "89Zr-labeled PSMA ligands for pharmacokinetic PET imaging and dosimetry of PSMA-617 and PSMA-I&T: a preclinical evaluation and first in man." European Journal of Nuclear Medicine and Molecular Imaging 49.6 (2022): 2064-2076.

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