68Ga]Ga-FAPI-46 PET for non-invasive detection of pulmonary fibrosis disease activity.

Abstract

The lack of effective molecular biomarkers to monitor idiopathic pulmonary fibrosis (IPF) activity or treatment response remains an unmet clinical need. Herein, we determined the utility of fibroblast activation protein inhibitor for positron emission tomography (FAPI PET) imaging in a mouse model of pulmonary fibrosis. Pulmonary fibrosis was induced by intratracheal administration of bleomycin (1 U/kg) while intratracheal saline was administered to control mice. Subgroups from each cohort (n = 3-5) underwent dynamic 1h PET/CT after intravenously injecting FAPI-46 radiolabeled with gallium-68 ([68Ga]Ga-FAPI-46) at 7days and 14days following disease induction. Animals were sacrificed following imaging for ex vivo gamma counting and histologic correlation. [68Ga]Ga-FAPI-46 uptake was quantified and reported as percent injected activity per cc (%IA/cc) or percent injected activity (%IA). Lung CT density in Hounsfield units (HU) was also correlated with histologic examinations of lung fibrosis. CT only detected differences in the fibrotic response at 14days post-bleomycin administration. [68Ga]Ga-FAPI-46 lung uptake was significantly higher in the bleomycin group than in control subjects at 7days and 14days. Significantly (P = 0.0012) increased [68Ga]Ga-FAPI-46 lung uptake in the bleomycin groups at 14days (1.01 ± 0.12%IA/cc) vs. 7days (0.33 ± 0.09%IA/cc) at 60min post-injection of the tracer was observed. These findings were consistent with an increase in both fibrinogenesis and FAP expression as seen in histology. CT was unable to assess disease activity in a murine model of IPF. Conversely, FAPI PET detected both the presence and activity of lung fibrogenesis, making it a promising tool for assessing early disease activity and evaluating the efficacy of therapeutic interventions in lung fibrosis patients.