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Abstract：
BACKGROUND: In the last decade the development of new PSMA-ligand based radiopharmaceuticals for the imaging and therapy of prostate cancer has been a highly active and important area of research. The most promising derivative in terms of interaction with the antigen and clinical properties has been found to be \"PSMA-617\", and its lutetium-177 radiolabelled version has recently been approved by EU and USA regulatory agencies for therapeutic purposes. For the above reasons, the development of new derivatives of PSMA-617 radiolabelled with fluorine-18 may still be of great interest. This paper proposes the comparison of two different PSMA-617 derivatives functionalized with NODA and RESCA chelators, respectively, radiolabelled via [18F]AlF2+ complexation.
RESULTS: The organic synthesis of two PSMA-617 derivatives and their radiolabelling via [18F]AlF2+ complexation resulted to proceed efficiently and successfully. Moreover, stability in solution and in plasma has been evaluated. The whole radiosynthesis procedure has been fully automated, and the final products have been obtained with radiochemical yield and purity potentially suitable for clinical studies. The biodistribution of the two derivatives was performed both in prostate cancer and glioma tumour models. Compared with the reference [18F]F-PSMA-1007 and [18F]F-PSMA-617-RESCA, [18F]F-PSMA-617-NODA derivative showed a higher uptake in both tumors, faster clearance in non-target organs, and lower uptake in salivary glands.
CONCLUSIONS: PSMA-617 NODA and RESCA derivatives were radiolabelled successfully via [18F]AlF2+ chelation, the former being more stable in solution and human plasma. Moreover, preclinical biodistribution studies showed that [18F]F-PSMA-617-NODA might be of potential interest for clinical applications.
RESULTS: The organic synthesis of two PSMA-617 derivatives and their radiolabelling via [18F]AlF2+ complexation resulted to proceed efficiently and successfully. Moreover, stability in solution and in plasma has been evaluated. The whole radiosynthesis procedure has been fully automated, and the final products have been obtained with radiochemical yield and purity potentially suitable for clinical studies. The biodistribution of the two derivatives was performed both in prostate cancer and glioma tumour models. Compared with the reference [18F]F-PSMA-1007 and [18F]F-PSMA-617-RESCA, [18F]F-PSMA-617-NODA derivative showed a higher uptake in both tumors, faster clearance in non-target organs, and lower uptake in salivary glands.
CONCLUSIONS: PSMA-617 NODA and RESCA derivatives were radiolabelled successfully via [18F]AlF2+ chelation, the former being more stable in solution and human plasma. Moreover, preclinical biodistribution studies showed that [18F]F-PSMA-617-NODA might be of potential interest for clinical applications.
摘要：
背景:在过去的十年中,用于前列腺癌的成像和治疗的新的基于PSMA配体的放射性药物的开发已经成为高度活跃和重要的研究领域。在与抗原相互作用和临床特性方面，最有前途的衍生物是“PSMA-617”，最近，欧盟和美国监管机构批准了其放射性标记的Luttium-177版本，用于治疗目的。由于上述原因,用氟-18放射性标记的PSMA-617的新衍生物的开发可能仍有很大的兴趣。本文提出了用NODA和RESCA螯合剂官能化的两种不同的PSMA-617衍生物的比较，分别,通过[18F]AlF2+络合进行放射性标记。
结果：两种PSMA-617衍生物的有机合成及其通过[18F]AlF2络合的放射性标记导致有效和成功地进行。此外，在溶液和血浆中的稳定性进行了评估。整个放射合成程序已经完全自动化，最终产品的放射化学产率和纯度可能适合临床研究。在前列腺癌和神经胶质瘤肿瘤模型中都进行了两种衍生物的生物分布。与参考[18F]F-PSMA-1007和[18F]F-PSMA-617-RESCA相比，[18F]F-PSMA-617-NODA衍生物在两种肿瘤中均显示出较高的摄取，在非靶器官中清除更快，唾液腺的摄取较低。
结论：PSMA-617NODA和RESCA衍生物通过[18F]AlF2螯合被成功地放射性标记，前者在溶液和人血浆中更稳定。此外，临床前生物分布研究表明，[18F]F-PSMA-617-NODA可能对临床应用具有潜在的兴趣。
结果：两种PSMA-617衍生物的有机合成及其通过[18F]AlF2络合的放射性标记导致有效和成功地进行。此外，在溶液和血浆中的稳定性进行了评估。整个放射合成程序已经完全自动化，最终产品的放射化学产率和纯度可能适合临床研究。在前列腺癌和神经胶质瘤肿瘤模型中都进行了两种衍生物的生物分布。与参考[18F]F-PSMA-1007和[18F]F-PSMA-617-RESCA相比，[18F]F-PSMA-617-NODA衍生物在两种肿瘤中均显示出较高的摄取，在非靶器官中清除更快，唾液腺的摄取较低。
结论：PSMA-617NODA和RESCA衍生物通过[18F]AlF2螯合被成功地放射性标记，前者在溶液和人血浆中更稳定。此外，临床前生物分布研究表明，[18F]F-PSMA-617-NODA可能对临床应用具有潜在的兴趣。
