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

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

doi:10.1126/scitranslmed.aaf4696

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

Sci Transl Med. 2017 Apr 5;9(384):eaaf4696. doi: 10.1126/scitranslmed.aaf4696.

Authors

Affiliations

¹ Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA.
² Division of Thoracic Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
³ Division of Pulmonary and Critical Care Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
⁴ Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
⁵ Biogen, Cambridge, MA 02142, USA.
⁶ Division of Surgical Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
⁷ Division of Thoracic Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA. [email protected] [email protected].
⁸ Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA. [email protected] [email protected].

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.

Publication types

Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, N.I.H., Extramural

MeSH terms

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*
Pulmonary Fibrosis / diagnostic imaging*
Pulmonary Fibrosis / pathology

Substances

Collagen Type I
Gallium Radioisotopes
Molecular Probes
Bleomycin

Abstract

Publication types

MeSH terms

Substances

Grants and funding