Data from Development and Application of Radioactive Ligands Targeting Fibroblasts with Albumin-Binding Sites

Abstract Fibroblast activation protein (FAP) is overexpressed on cancer-associated fibroblasts, making it an important target for cancer diagnosis and treatment, but limited tumor retention hinders late-stage diagnosis and radionuclide therapy. In this study, three albumin-bound FAP inhibitor (FAPI) radioligands, ⁶⁸Ga/¹⁷⁷Lu-DOTA-ALB-01, ⁶⁸Ga/¹⁷⁷Lu-DOTA-ALB-02, and ⁶⁸Ga/¹⁷⁷Lu-DOTA-ALB-03, were synthesized and evaluated for their in vitro stability, binding affinity, in vivo biodistribution, and tumor uptake using ⁶⁸Ga and ¹⁷⁷Lu labeling. All radioligands are stable in saline and plasma and exhibit high FAP-binding affinity. ¹⁷⁷Lu-DOTA-ALB-02 has longer retention in circulation than ¹⁷⁷Lu-FAPI-46 and other radioligands. Continuous tumor accumulation was observed during imaging with both ¹⁷⁷Lu-DOTA-ALB-01 and ¹⁷⁷Lu-DOTA-ALB-02. Notably, ¹⁷⁷Lu-DOTA-ALB-02 had a significant tumor/nontarget ratio as indicated by biodistribution data. The outstanding tumor retention properties of ¹⁷⁷Lu-DOTA-ALB-02 have been demonstrated in small-animal single-photon emission computed tomography imaging and biodistribution studies; therefore, it is considered the albumin-binding FAPI with the most favorable pharmacokinetic and imaging properties, worthy of further clinical investigation.