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.

• Authors: Pauline Désogère, Luis F Tapias, Lida P Hariri, Nicholas J Rotile, Tyson A Rietz, Clemens K Probst, Francesco Blasi, Helen Day, Mari Mino-Kenudson, Paul Weinreb, Shelia M Violette, Bryan C Fuchs, Andrew M Tager, Michael Lanuti, Peter Caravan
• Journal: Science translational medicine (Sci Transl Med) Vol. 9 Issue 384 (04 05 2017) ISSN: 1946-6242 [Electronic] United States
• PMID: 28381537 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2017, American Association for the Advancement of Science.

Chemical References

• Collagen Type I
• Gallium Radioisotopes
• Molecular Probes
• Bleomycin

Topics

• Animals
• Bleomycin
• Capillary Permeability
• Collagen Type I (metabolism)
• Disease Models, Animal
• Disease Progression
• Gallium Radioisotopes
• Humans
• Idiopathic Pulmonary Fibrosis (pathology)
• Kidney (metabolism)
• Lung (pathology)
• Male
• Mice, Inbred C57BL
• Molecular Probes (chemistry)
• Positron-Emission Tomography
• Pulmonary Fibrosis (diagnosis, diagnostic imaging, pathology)