title: 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 evaluated68Ga-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 lung68Ga-CBP8 uptake (quantified ex vivo) correlated linearly (r2= 0.80) with the amount of lung collagen in mice with fibrosis. We further demonstrated that the68Ga-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 that68Ga-CBP8 is a promising candidate for noninvasive imaging of human pulmonary fibrosis.
authors.affiliation: Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA.
authors.forename: Pauline
authors.identifier: 0000-0001-8620-4108
authors.initials: P
authors.lastname: Désogère
authors.affiliation: Division of Thoracic Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
authors.forename: Luis F
authors.identifier: 0000-0003-0064-460X
authors.initials: LF
authors.lastname: Tapias
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.|Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
authors.forename: Lida P
authors.initials: LP
authors.lastname: Hariri
authors.affiliation: Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Rotile
authors.affiliation: Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA.
authors.forename: Tyson A
authors.identifier: 0000-0003-4670-5279
authors.initials: TA
authors.lastname: Rietz
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
authors.forename: Clemens K
authors.identifier: 0000-0002-5546-9143
authors.initials: CK
authors.lastname: Probst
authors.affiliation: Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA.
authors.forename: Francesco
authors.initials: F
authors.lastname: Blasi
authors.affiliation: Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA.
authors.forename: Helen
authors.initials: H
authors.lastname: Day
authors.affiliation: Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
authors.forename: Mari
authors.identifier: 0000-0002-9092-2265
authors.initials: M
authors.lastname: Mino-Kenudson
authors.affiliation: Biogen, Cambridge, MA 02142, USA.
authors.forename: Paul
authors.identifier: 0000-0002-0802-0052
authors.initials: P
authors.lastname: Weinreb
authors.affiliation: Biogen, Cambridge, MA 02142, USA.
authors.forename: Shelia M
authors.initials: SM
authors.lastname: Violette
authors.affiliation: Division of Surgical Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
authors.forename: Bryan C
authors.initials: BC
authors.lastname: Fuchs
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
authors.forename: Andrew M
authors.identifier: 0000-0002-5826-918X
authors.initials: AM
authors.lastname: Tager
authors.affiliation: Division of Thoracic Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA. caravan@nmr.mgh.harvard.edu mlanuti@mgh.harvard.edu.
authors.forename: Michael
authors.initials: M
authors.lastname: Lanuti
authors.affiliation: Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA. caravan@nmr.mgh.harvard.edu mlanuti@mgh.harvard.edu.
authors.forename: Peter
authors.identifier: 0000-0002-3179-6537
authors.initials: P
authors.lastname: Caravan
mesh_terms: D000818:Animals; D001761:Bleomycin; D002199:Capillary Permeability; D024042:Collagen Type I / Q000378:metabolism*; D004195:Disease Models, Animal; D018450:Disease Progression; D005710:Gallium Radioisotopes; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000473:pathology; D007668:Kidney / Q000378:metabolism; D008168:Lung / Q000473:pathology; D008297:Male; D008810:Mice, Inbred C57BL; D015335:Molecular Probes / Q000737:chemistry*; D049268:Positron-Emission Tomography; D011658:Pulmonary Fibrosis / Q000175:diagnosis* / Q000000981:diagnostic imaging* / Q000473:pathology
chemical_list: D024042:Collagen Type I; D005710:Gallium Radioisotopes; D015335:Molecular Probes; D001761:Bleomycin