18F]AlF-CBP imaging of type I collagen for non-invasive monitoring of pulmonary fibrosis in preclinical models.

Abstract

Pulmonary fibrosis is an irreversible scar-forming condition for which there is a lack of non-invasive and specific methods for monitoring its progression and therapy efficacy. However, the disease is known to be accompanied by collagen accumulation. Here, we developed a novel positron emission tomography (PET) probe targeting type I collagen to evaluate its utility for the non-invasive assessment of pulmonary fibrosis. We designed a 18F-labeled PET probe ([18F]AlF-CBP) to target type I collagen and evaluated its binding affinity, specificity and stability in vitro. PET with [18F]AlF-CBP, CT, histopathology, immunofluorescence, and biochemical indice were performed to assess and quantify type I collagen levels and pulmonary fibrosis progression and treatment in murine models. Dynamic PET/CT studies of [18F]AlF-CBP were conducted to assess lung fibrosis in non-human primate models. [18F]AlF-CBP was successfully prepared, and in vitro and in vivo tests showed high stability (> 95%) and type I collagen specificity (IC50 = 0.36 µM). The lungs of the fibrotic murine model showed more elevated probe uptake and retention compared to the control group, and there was a positive correlation between the radioactivity uptake signals and the degree of fibrosis (CT: R2 = 0.89, P < 0.0001; hydroxyproline levels: R2 = 0.89, P < 0.0001). PET signals also correlated well with mean lung density in non-human primate models of pulmonary fibrosis (R2 = 0.84, P < 0.0001). [18F]AlF-CBP PET imaging is a promising non-invasive method for specific monitoring of lung fibrosis progression and therapy efficacy.