Preclinical evaluation of DOTAGA.Glu.(FAPI)₂ and DO3A.Glu.(FAPI)₂ as theranostics with human dosimetry extrapolation to lutetium-177 and terbium-161 analogs.

ABSTRACT:

Purpose

This study aims to assess DOTAGA.Glu.(FAPI)₂ and DO3A.Glu.(FAPI)₂, specifically engineered as precursors for the development of theranostic FAPI-targeted radioligands.

Methods

DOTAGA.Glu.(FAPI)₂ and DO3A.Glu.(FAPI)₂ were radiolabeled with gallium-68 and lutetium-177, followed by in vitro (lipophilicity, protein binding, saturation, internalization and externalization) studies on FAP⁺ CAFs. In vivo (biodistribution, metabolic stability, blood kinetics, PET/SPECT/CT imaging) and ex vivo, (autoradiography, immunohistochemistry) conducted on PC3-mice. Murine dosimetry data were extrapolated to human estimates.

Results

All radioligands achievied > 98% radiochemical purity, demonstrating high FAP affinity (K

SUBMITTER: Bilinska A 

PROVIDER: S-EPMC12860872 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature