Preclinical evaluation of [68Ga]Ga-AAZTA-FAPI-46: a novel PET tracer for targeting fibroblast activation protein (FAP)

EJNMMI Radiopharm Chem. 2025 Aug 5;10(1):51. doi: 10.1186/s41181-025-00375-2.

Abstract

Background: The aim of this work was to demonstrate the suitability of AAZTA chelator conjugated to a FAPI-46-derived FAP inhibitor and labelled with gallium-68 as a potential PET tracer.

Results: Gallium-68 radiolabelling was achieved with high radiochemical yield at room temperature. The new tracer was stable in different media, showing specific binding to FAP-protein both in vitro and in vivo, and a suitable biodistribution and clearance. High tumor uptake of the tracer (1.01 ± 0.12 SUV 35 min p.i.) was found in 4T1-tumor bearing mice, and blocking experiments demonstrated the high target specificity.

Conclusion: The substitution of the DOTA chelator with the AAZTA ligand on FAPI-46 moiety allowed a fast radiolabelling at room temperature of the PET tracer without influencing the biodistribution properties, such as clearance and FAP-mediated tumor uptake, but rather expanding the tracer applicability.

Keywords: AAZTA; FAP; FAPI-46; GALLIUM-68; PET.