Molecular Magnetic Resonance Imaging of Lung Fibrogenesis with an Oxyamine-Based Probe

Angew Chem Int Ed Engl. 2017 Aug 7;56(33):9825-9828. doi: 10.1002/anie.201704773. Epub 2017 Jul 13.

Abstract

Fibrogenesis is the active production of extracellular matrix in response to tissue injury. In many chronic diseases persistent fibrogenesis results in the accumulation of scar tissue, which can lead to organ failure and death. However, no non-invasive technique exists to assess this key biological process. All tissue fibrogenesis results in the formation of allysine, which enables collagen cross-linking and leads to tissue stiffening and scar formation. We report herein a novel allysine-binding gadolinium chelate (GdOA), that can non-invasively detect and quantify the extent of fibrogenesis using magnetic resonance imaging (MRI). We demonstrate that GdOA signal enhancement correlates with the extent of the disease and is sensitive to a therapeutic response.

Keywords: aldehydes; allysine; collagen; fibrosis; imaging agents.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • 2-Aminoadipic Acid / analogs & derivatives
  • 2-Aminoadipic Acid / chemistry
  • Amines / chemistry*
  • Animals
  • Bleomycin
  • Chelating Agents / chemistry*
  • Gadolinium / chemistry
  • Magnetic Resonance Imaging*
  • Mice
  • Molecular Conformation
  • Molecular Probes / chemistry*
  • Pulmonary Fibrosis / chemically induced
  • Pulmonary Fibrosis / diagnosis*

Substances

  • Amines
  • Chelating Agents
  • Molecular Probes
  • Bleomycin
  • 2-Aminoadipic Acid
  • allysine
  • Gadolinium