Preliminary in-vivo evaluation of [ 68 Ga]Ga-FAPI-46 in a fibroblast activation protein-negative breast cancer model

Fibroblast activation protein (FAP), which is abundantly expressed in cancer-associated fibroblasts, is an attractive target for tumour imaging and therapy. [ 68 Ga]Ga-FAPI-46, a gallium-68-labelled FAP inhibitor, has demonstrated favourable pharmacokinetics for PET. This study evaluated the radiolabelling efficiency, stability, and biodistribution of [ 68 Ga]Ga-FAPI-46 in a breast cancer mouse model using MCF-7 cell line, which is known to lack FAP expression.

[ 68 Ga]Ga-FAPI-46 was radiolabeled directly from FAPI-46 using 68 Ga in acetate buffer and analysed for radiochemical purity (RCP) by radio-TLC. Stability at room temperature was assessed up to 5 h post-radiolabeling. Biodistribution studies were conducted in female BALB/c nude mice with MCF-7 tumours. Organ uptake was determined 1 h after injection and expressed as a percentage of injected dose per gramme of tissue (%ID/g). A comparative study between [ 68 Ga]Ga-FAPI-46 and free 68 Ga was also performed.

[ 68 Ga]Ga-FAPI-46 consistently achieved high RCP values (>95%, maximum 99.1%) and remained stable for up to 5 h without added radioprotectant. At 1 h, [ 68 Ga]Ga-FAPI-46 showed higher uptake in kidneys (4.15%ID/g), heart (3.59%ID/g), and liver (1.70%ID/g), and low uptake in muscle (0.31%ID/g) and bone (0.57%ID/g). Mean tumour uptake was low (0.92%ID/g), consistent with the FAP-negative status of MCF-7 cells. In contrast, free 68 Ga showed a non-specific distribution in blood (29.13%ID/g), lungs (18.50%ID/g), and bone (13.37%ID/g).

[ 68 Ga]Ga-FAPI-46 showed efficient radiolabelling with high RCP and short-term stability. Its low accumulation in FAP-negative tumours supports tracer selectivity and provides a baseline for comparative studies in FAP-expressing tumour models.