FAP-targeted delivery of radioiodinated probes: A progressive albumin-driven strategy for tumor theranostics

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 [¹³¹I]IPB-FAPI, [¹³¹I]IPB-FAPI-A1, [¹³¹I]IPB-FAPI-A3, [¹³¹I]FSDD₃I) 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 [¹³¹I]FSDD₃I 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 [¹³¹I]FSDD₃I 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, ¹³¹I-labeled FSDD₃I ([¹³¹I]FSDD₃I) emerged as a standout candidate with superior competitive advantages for application in radioiodine-guided internal irradiation therapy.