Luo Yihui, Xu Yu, Li Wenjin, Hua Yuqi, Shen Qiaoling, Wang Jialiang, Chen Liping, Fu Haitian, Lin Jianguo, Yu Chunjing
Department of Nuclear Medicine, Affiliated Hospital of Jiangnan University, Wuxi 214125, China.
Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu 214122, China.
J Med Chem. 2025 Jun 26;68(12):12745-12755. doi: 10.1021/acs.jmedchem.5c00637. Epub 2025 Jun 11.
A suitable theranostic molecule targeting the fibroblast activation protein (FAP) might provide individualized and precise diagnostic and therapeutic solutions for patients with FAP-positive tumors. In this study, a FAP-targeted molecule, FAPI-JNU, was developed with picomolar affinity for FAP. [Ga]Ga/[Lu]Lu-FAPI-JNU was synthesized and verified by HPLC, demonstrating high radiochemical purity (>95%) and yield (>90%). Favorable biodistribution and tumor-targeting specificity of [Ga]Ga-FAPI-JNU were determined in tumor-bearing mice expressing FAP ( = 4), with higher tumor uptake observed compared to [Ga]Ga-FAPI-46. Clinical PET/CT imaging with [Ga]Ga-FAPI-JNU showed superior detection of lymph node metastases, bone metastases, and recurrent lesions compared to [F]F-FDG ( = 9). [Lu]Lu-FAPI-JNU demonstrated effective tumor targeting and inhibition of tumor development in tumor-bearing mice, with the high radio-dosage group (46 MBq/mouse, = 6) showing significant antitumor efficacy compared to the blank control group. The developed radiopharmaceuticals, [Ga]Ga/[Lu]Lu-FAPI-JNU, show potential for clinical use in diagnostic imaging and tumor therapy through FAP targeting.
一种合适的靶向成纤维细胞活化蛋白（FAP）的诊疗分子可能为FAP阳性肿瘤患者提供个性化且精确的诊断和治疗方案。在本研究中，开发了一种对FAP具有皮摩尔亲和力的靶向FAP的分子FAPI-JNU。合成了[镓]Ga/[镥]Lu-FAPI-JNU并通过高效液相色谱法进行验证，显示出高放射化学纯度（>95%）和产率（>90%）。在表达FAP的荷瘤小鼠（n = 4）中确定了[镓]Ga-FAPI-JNU良好的生物分布和肿瘤靶向特异性，与[镓]Ga-FAPI-46相比观察到更高的肿瘤摄取。与[氟]F-FDG（n = 9）相比，[镓]Ga-FAPI-JNU的临床PET/CT成像显示对淋巴结转移、骨转移和复发灶的检测效果更佳。[镥]Lu-FAPI-JNU在荷瘤小鼠中显示出有效的肿瘤靶向性并抑制肿瘤发展，高放射剂量组（46 MBq/小鼠，n = 6）与空白对照组相比显示出显著的抗肿瘤疗效。所开发的放射性药物[镓]Ga/[镥]Lu-FAPI-JNU通过靶向FAP在诊断成像和肿瘤治疗中显示出临床应用潜力。
