Am J Respir Cell Mol Biol. 2013 Aug 10. doi: 10.1165/rcmb.2013-0039OC. [Epub ahead of print]

Molecular MR Imaging of Pulmonary Fibrosis in Mice

Caravan P, Yang Y, Zachariah R, Schmitt A, Mino-Kenudson M, Chen HH, Sosnovik DE, Dai G, Fuchs BC, Lanuti M.

Abstract

Rationale: Idiopathic pulmonary fibrosis is a chronic, progressive fibrosing interstitial pneumonia of unknown cause resulting in dyspnea and functional decline until death. There are currently no effective noninvasive tools to monitor disease progression and response to treatment. Objective: To determine whether molecular magnetic resonance imaging (MRI) of the lung using a probe targeted to type I collagen could provide a direct, non-invasive method for assessment of pulmonary fibrosis in a mouse model. Methods: Pulmonary fibrosis was generated in mice by transtracheal instillation of bleomycin. Six cohorts were imaged prior to and immediately following i.v. administration of molecular imaging probe: 1) bleomycin + collagen-targeted probe EP-3533; 2) sham + EP-3533; 3) bleomycin + non-binding control probe EP-3612; 4) sham + EP-3612; 5) bleomycin + EP-3533 imaged early; 6) bleomycin + EP-3533 imaged late. Signal:noise (SNR) enhancement was quantified in the lungs and muscle. Lung tissue was subjected to pathologic scoring of fibrosis and analyzed for gadolinium and hydroxyproline. Measurements and main results: Bleomycin treated mice had 35% higher lung collagen than sham mice, p

PMID: 23927643