Tang Ganghua, Zhang Rongqin, Zhang Xiaojun, Chen KeYin, Gong Fengping, Huang Yanchao, Zhang Zhanwen, Huang Jiawen
Key Laboratory Project of Guangdong Provincial Department of Education for Ordinary Universities and GDMPA Key Laboratory for Quality Control and Evaluation of Radiopharmaceuticals, Department of Nuclear Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province 510515, China.
School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, Guangdong Province 510515, China.
J Med Chem. 2025 May 22;68(10):9973-9983. doi: 10.1021/acs.jmedchem.4c02961. Epub 2025 May 2.
FAPI-PET/CT has become a promising tool for cancer diagnosis. However, the pharmacokinetic properties of FAPI tracers need optimization. Here, we developed a novel FAPI tracer, [F]AlF-NOTA-SPA-FAPT, for cancer imaging. NOTA-SPA-FAPT was successfully synthesized and radiolabeled with a high radiochemical purity. [F]AlF-NOTA-SPA-FAPT displayed satisfying stability, hydrophilicity, and affinity to FAP, as well as specific uptake in A549-FAP cells. Micro-PET/CT showed that [F]AlF-NOTA-SPA-FAPT is rapidly excreted through the renal system. [F]AlF-NOTA-SPA-FAPT exhibited high tumor uptake and excellent retention, showing better tumor delineation compared to [F]FDG and [F]AlF-NOTA-FAPI-42. Pilot clinical studies of [F]AlF-NOTA-SPA-FAPT and head-to-head comparison with [F]FDG were performed on 13 cancer patients. Compared to [F]FDG, [F]AlF-NOTA-SPA-FAPT had higher uptake in primary tumor and lymph node metastases as well as favorable distribution and good tumor retention. In conclusion, [F]AlF-NOTA-SPA-FAPT demonstrated high tumor accumulation, as well as improved pharmacokinetic properties. [F]AlF-NOTA-SPA-FAPT could emerge as a promising alternative to the currently established FAPI tracers.
FAPI-PET/CT已成为一种很有前景的癌症诊断工具。然而，FAPI示踪剂的药代动力学特性需要优化。在此，我们开发了一种新型FAPI示踪剂[F]AlF-NOTA-SPA-FAPT用于癌症成像。NOTA-SPA-FAPT成功合成并以高放射化学纯度进行了放射性标记。[F]AlF-NOTA-SPA-FAPT表现出令人满意的稳定性、亲水性以及对FAP的亲和力，并且在A549-FAP细胞中有特异性摄取。微型PET/CT显示[F]AlF-NOTA-SPA-FAPT通过肾脏系统迅速排泄。[F]AlF-NOTA-SPA-FAPT表现出高肿瘤摄取和出色的滞留性，与[F]FDG和[F]AlF-NOTA-FAPI-42相比，肿瘤轮廓显示更佳。对13例癌症患者进行了[F]AlF-NOTA-SPA-FAPT的初步临床研究以及与[F]FDG的直接对比。与[F]FDG相比，[F]AlF-NOTA-SPA-FAPT在原发性肿瘤和淋巴结转移灶中有更高的摄取，以及良好的分布和肿瘤滞留性。总之，[F]AlF-NOTA-SPA-FAPT显示出高肿瘤蓄积以及改善的药代动力学特性。[F]AlF-NOTA-SPA-FAPT可能成为目前已确立的FAPI示踪剂的一种有前景的替代物。
