Design and Biological Evaluation of FAP-Man, a Mannosylated FAP-Targeted Radioglycopeptide for Tumor Imaging and Radionuclide Therapy
Miaomiao Song, Entao Liu, Rui Cao, Luming Sun, Peng Wang, Shuang Duan, Ji Tao, Long Qiu, Jin Du, Ning Liu, Feize Li, Chunrong Qu, Lei Jiang, Zhen ChengAbstract
Fibroblast activation protein (FAP) is an attractive target for radiotheranostic development because of its abundant expression in tumor-associated fibroblasts and limited distribution in normal tissues. Here, we developed FAP-Man, a mannosylated FAP-targeted radioglycopeptide based on the FAP-2286 scaffold, to optimize tumor targeting and pharmacokinetic properties. Compared with [68Ga]Ga-FAP-2286, [68Ga]Ga-FAP-Man showed higher tumor uptake in U87MG tumor-bearing mice (16.917 ± 4.986 vs 3.188 ± 0.535 %ID/g at 1 h post-injection) and improved tumor-to-liver contrast. Both [177Lu]Lu-FAP-Man and [225Ac]Ac-FAP-Man significantly inhibited tumor growth compared with PBS-treated controls. Preliminary clinical PET imaging further supported its potential for favorable lesion visualization and lesion-to-background contrast, particularly for hepatic lesions. These findings support further evaluation of FAP-Man as a FAP-targeted radiopharmaceutical candidate.