Type I collagen–targeted PET probe for pulmonary fibrosis detection and staging in preclinical models

Abstract

Pulmonary fibrosis is scarring of the lungs that can arise from radiation injury, drug toxicity, environmental or genetic causes, and for unknown reasons [idiopathic pulmonary fibrosis (IPF)]. Overexpression of collagen is a hallmark of organ fibrosis. We describe a peptide-based positron emission tomography (PET) probe (⁶⁸Ga-CBP8) that targets collagen type I. We evaluated ⁶⁸Ga-CBP8 in vivo in the bleomycin-induced mouse model of pulmonary fibrosis. ⁶⁸Ga-CBP8 showed high specificity for pulmonary fibrosis and high target/background ratios in diseased animals. The lung PET signal and lung ⁶⁸Ga-CBP8 uptake (quantified ex vivo) correlated linearly (r² = 0.80) with the amount of lung collagen in mice with fibrosis. We further demonstrated that the ⁶⁸Ga-CBP8 probe could be used to monitor response to treatment in a second mouse model of pulmonary fibrosis associated with vascular leak. Ex vivo analysis of lung tissue from patients with IPF supported the animal findings. These studies indicate that ⁶⁸Ga-CBP8 is a promising candidate for noninvasive imaging of human pulmonary fibrosis.