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.
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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Authors: 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 Journal: Eur J Nucl Med Mol Imaging Date: 2021-12-21 Impact factor: 10.057
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Authors: Florian C Gaertner; Khalil Halabi; Hojjat Ahmadzadehfar; Stefan Kürpig; Elisabeth Eppard; Charalambos Kotsikopoulos; Nikolaos Liakos; Ralph A Bundschuh; Holger Strunk; Markus Essler Journal: Oncotarget Date: 2017-07-06
Authors: Bastiaan M Privé; Marcel J R Janssen; Inge M van Oort; Constantijn H J Muselaers; Marianne A Jonker; Michel de Groot; Niven Mehra; J Fred Verzijlbergen; Tom W J Scheenen; Patrik Zámecnik; Jelle O Barentsz; Martin Gotthardt; Walter Noordzij; Wouter V Vogel; Andries M Bergman; Henk G van der Poel; André N Vis; Daniela E Oprea-Lager; Winald R Gerritsen; J Alfred Witjes; James Nagarajah Journal: BMC Cancer Date: 2020-09-14 Impact factor: 4.430
Authors: Mehmet Erdogan; Sevim S Sengul; Bulent Cetin; Mustafa Avcı; Samet Yagci; Ismail Ozkoç; Damla Ezgi Barikan; Mustafa Yildiz Journal: Ann Nucl Med Date: 2022-04-09 Impact factor: 2.668
Authors: 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 Journal: Eur J Nucl Med Mol Imaging Date: 2021-12-21 Impact factor: 10.057