Research ArticlePulmonary fibrosis

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

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Science Translational Medicine  05 Apr 2017:
Vol. 9, Issue 384, eaaf4696
DOI: 10.1126/scitranslmed.aaf4696

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Focusing on fibrosis

Although fibrosis is known to play a role in the progression of multiple diseases, affecting heart, lung, liver, and skin, among other organs, it remains difficult to visualize and diagnose noninvasively. To address this, Désogère and colleagues developed an imaging probe for positron emission tomography that detects type I collagen, an extracellular matrix protein present in fibrotic tissues. The probe detected fibrotic lung tissue in two mouse models of bleomycin-induced pulmonary fibrosis and in samples of human lungs from patients with idiopathic pulmonary fibrosis, where higher probe uptake correlated with regions of increasing fibrosis.

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.

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