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

## TL;DR

This study introduces a new PET tracer that targets fibroblast activation protein and shows high tumor uptake in mice.

## Contribution

The novel use of the AAZTA chelator enables fast room-temperature radiolabelling without affecting tracer performance.

## Key findings

- The tracer showed high radiochemical yield and stability in various media.
- It demonstrated specific FAP-targeted tumor uptake in 4T1 tumor-bearing mice.
- The tracer's biodistribution and clearance were suitable for PET imaging.

## Abstract

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.

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.

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.

The online version contains supplementary material available at 10.1186/s41181-025-00375-2.