FAP-targeted delivery of radioiodinated probes: A progressive albumin-driven strategy for tumor theranostics
Huifeng Li, Dongsheng Xia, Lingxin Meng, Jingru Zhang, Xuedong Chen, Rongqiang Zhuang, Jinxiong Huang, Yesen Li, Jianyang Fang, Xianzhong Zhang, Zhide Guo
Abstract
Fibroblasts activated protein (FAP) appears to be a promising target for tumor theranostics. However, the development of radioiodinated probes for FAP has been slow. In this study, a progressive abumin-driven strategy was adopted to improve the FAP-targeted delivery of radioiodinated probes for tumor theranostics. A series of FAP-targeted probes (namely [ 131 I]IPB-FAPI, [ 131 I]IPB-FAPI-A1, [ 131 I]IPB-FAPI-A3, [ 131 I]FSDD 3 I) were synthesized by incorporating an albumin-binding moiety (4-( p -iodophenyl)butyric acid, 4-IPBA) labeled with radioiodine . The specificity and binding characteristics of the radiotracers to FAP and human serum albumin (HSA) were confirmed. SPECT imaging results showed that the [ 131 I]FSDD 3 I had more prominent tumor retention property and superior target-to-nontarget ratio, which were consistent with the biodistribution results. As expected, the FAP-targeted therapy with 11.1 MBq [ 131 I]FSDD 3 I significantly inhibited tumor growth. In conclusion, this proof-of-concept study employed a progressive design strategy to enhance pharmacokinetics of radioiodinated FAP-targeted probes. Among these radioiodinated FAPI probes, 131 I-labeled FSDD 3 I ([ 131 I]FSDD 3 I) emerged as a standout candidate with superior competitive advantages for application in radioiodine-guided internal irradiation therapy.