Zhang Qingyu, Hu Zhoumi, Zhao Haitao, Du Fuqiang, Lv Chun, Peng Tukang, Zhang Yukai, Zhang Bowu, Liu Jianjun, Wang Cheng
Department of Nuclear Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China.
MOE Key Lab of Resource Chemistry, Joint International Research Laboratory of Resource Chemistry of Ministry of Education, Shanghai Key Laboratory of Rare Earth Functional Materials, and Shanghai Frontiers Science Centre of Biomimetic Catalysis, Shanghai Normal University, Shanghai 200234, China.
Pharmaceuticals (Basel). 2025 Feb 19;18(2):277. doi: 10.3390/ph18020277.
Cancer-associated fibroblasts (CAFs) are key contributors to the tumorigenic process, with fibroblast activation protein (FAP) overexpressed on CAFs in numerous epithelial carcinomas. FAP represents a promising target for tumor imaging and therapy. We aimed to develop a novel [F]AlF-HRESCA-FAPI radiotracer with a high labeling yield at room temperature for positron emission tomography (PET) imaging of FAP-expressing tumors. : The HRESCA-FAPI chelator was synthesized and radiolabeled with [F]AlF. Its radiotracer binding affinity to FAP was assessed using surface plasmon resonance (SPR). Its in vitro stability, plasma clearance, and biodistribution were evaluated. PET imaging was performed in U87MG tumor-bearing mice, with a blocking study to assess tracer specificity. : The [F]AlF-HRESCA-FAPI radiotracer demonstrated a high binding affinity to FAP (K < 10.09 pM) and favorable radiochemical yields (92.4 ± 2.4%) with >95% radiochemical purity. In vitro and in vivo studies showed good stability and rapid clearance from non-target tissues. PET imaging revealed specific tumor uptake, which was significantly reduced by co-injection with unlabeled DOTA-FAPI-04. : [F]AlF-HRESCA-FAPI is a promising radiotracer for PET imaging of FAP-expressing tumors. Further optimization of its pharmacokinetics could make it a potential candidate for clinical translation.
癌症相关成纤维细胞（CAFs）是肿瘤发生过程的关键促成因素，在众多上皮癌中，成纤维细胞活化蛋白（FAP）在CAFs上过度表达。FAP是肿瘤成像和治疗的一个有前景的靶点。我们旨在开发一种新型的[F]AlF-HRESCA-FAPI放射性示踪剂，其在室温下具有高标记产率，用于表达FAP的肿瘤的正电子发射断层扫描（PET）成像。：合成了HRESCA-FAPI螯合剂并用[F]AlF进行放射性标记。使用表面等离子体共振（SPR）评估其放射性示踪剂与FAP的结合亲和力。评估了其体外稳定性、血浆清除率和生物分布。在荷U87MG肿瘤的小鼠中进行PET成像，并进行阻断研究以评估示踪剂的特异性。：[F]AlF-HRESCA-FAPI放射性示踪剂对FAP表现出高结合亲和力（K<10.09 pM）和良好的放射化学产率（92.4±2.4%），放射化学纯度>95%。体外和体内研究显示出良好的稳定性以及从非靶组织的快速清除。PET成像显示出特异性肿瘤摄取，通过与未标记的DOTA-FAPI-04共同注射可显著降低。：[F]AlF-HRESCA-FAPI是用于表达FAP的肿瘤的PET成像的一种有前景的放射性示踪剂。进一步优化其药代动力学可使其成为临床转化的潜在候选者。
