Is Thiourea the Weak Link? An Investigation of the In Vitro and In Vivo Destabilization of [²⁰³Pb]- and [²¹²Pb]Pb²⁺ Thiourea-Based Bioconjugates.

ABSTRACT: Fibroblast activation protein (FAP) is overexpressed in a variety of cancers, making it an attractive target for bifunctional chelator-based radiopharmaceuticals. This study initially aimed to assess the effect of chelator structure on the biodistribution of ²⁰³Pb/²¹²Pb-labeled FAP inhibitor (FAPI) bioconjugates. However, suboptimal in vivo biodistribution and imaging results suggested the bioconjugate was unstable. RadioHPLC analysis of urine samples suggest the thiourea bond, formed during conjugation between an amine on the biomolecule, and an isothiocyanate-functionalized chelator, is unstable in vivo, resulting in detachment of the radiometal-chelator complex from the targeting vector, resulting in poor tumor accumulation. To determine whether this instability wa

SUBMITTER: McNeil BL 

PROVIDER: S-EPMC12921517 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature