Department of Medical Imaging, Nuclear Medicine, Radboud University Medical Center, PO Box 9101, 6500 HB, Nijmegen, The Netherlands.
Department of Nuclear Medicine, Saarland University Medical Center, Homburg, Germany.
Eur J Nucl Med Mol Imaging. 2022 May;49(6):2064-2076. doi: 10.1007/s00259-021-05661-0. Epub 2021 Dec 21.
Prolonged in vivo evaluation of PSMA tracers could improve tumor imaging and patient selection for Lu-PSMA-617 and Lu-PSMA-I&T. In this study, we present the radiolabeling method of PSMA-617 and PSMA-I&T with the long-lived positron emitter Zr to enable PET imaging up to 7 days post-injection. We compared the biodistribution of Zr-PSMA-617 and Zr-PSMA-I&T to those of Lu-PSMA-617 and Lu-PSMA-I&T, respectively, in a PSMA xenograft model. Moreover, we provide the first human Zr-PSMA-617 images.
PSMA ligands were labeled with 50-55 MBq [Zr]ZrCl 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 Zr-PSMA-617, Zr-PSMA-I&T, Lu-PSMA-617, or Lu-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 Zr-PSMA-617 followed by PET/CT imaging.
Zr-labeled PSMA ligands showed a comparable ex vivo biodistribution to its respective Lu-labeled counterparts with high tumor accumulation in the PSMA xenografts. However, using a dose estimation model for Lu, absorbed radiation dose in bone and kidneys differed among the Lu-PSMA and Zr-PSMA tracers. Zr-PSMA-617 PET in the first human patient showed high contrast of PSMA expressing tissues up to 48 h post-injection.
PSMA-617 and PSMA-I&T were successfully labeled with Zr and demonstrated high uptake in PSMA xenografts, which enabled PET up to 168 h post-injection. The biodistribution of Zr-PSMA-I&T and Zr-PSMA-617 resembled that of Lu-PSMA-I&T and Lu-PSMA-617, respectively. The first patient Zr-PSMA-617 PET images were of high quality warranting further clinical investigation.
延长 PSMA 示踪剂的体内评估可以改善肿瘤成像并为 Lu-PSMA-617 和 Lu-PSMA-I&T 选择合适的患者。在这项研究中，我们介绍了使用长半衰期正电子发射体 Zr 对 PSMA-617 和 PSMA-I&T 进行放射性标记的方法，从而可以在注射后长达 7 天进行 PET 成像。我们比较了 Zr-PSMA-617 和 Zr-PSMA-I&T 与 Lu-PSMA-617 和 Lu-PSMA-I&T 各自在 PSMA 异种移植模型中的生物分布。此外，我们提供了首例人类 Zr-PSMA-617 图像。
使用两步标记方案，用 50-55MBq[Zr]ZrCl 标记 PSMA 配体。为了进行生物分布研究，荷有 PSMA 和 PSMA 异种移植的 BALB/c 裸鼠静脉内接受 0.6μg（0.6-1MBq）的 Zr-PSMA-617、Zr-PSMA-I&T、Lu-PSMA-617 或 Lu-PSMA-I&T。在注射后长达 168 小时进行离体生物分布和 PET/SPECT 成像。从生物分布数据进行剂量估计。该患者接受了 90.5MBq Zr-PSMA-617，随后进行了 PET/CT 成像。
Zr 标记的 PSMA 配体与各自的 Lu 标记对应物具有相似的离体生物分布，在 PSMA 异种移植中具有较高的肿瘤摄取。然而，使用 Lu 的剂量估算模型，Lu-PSMA 和 Zr-PSMA 示踪剂的骨和肾脏吸收剂量不同。首例人类患者的 Zr-PSMA-617 PET 成像在注射后 48 小时内显示了高对比度的 PSMA 表达组织。
成功地用 Zr 标记了 PSMA-617 和 PSMA-I&T，并且在 PSMA 异种移植中显示出高摄取，从而可以在注射后长达 168 小时进行 PET 成像。Zr-PSMA-I&T 和 Zr-PSMA-617 的生物分布分别类似于 Lu-PSMA-I&T 和 Lu-PSMA-617。首例患者的 Zr-PSMA-617 PET 图像质量很高，值得进一步临床研究。
