Magnetic resonance molecular imaging of vascular cell adhesion molecule-1 expression in inflammatory lesions using a peptide-vectorized paramagnetic imaging probe

J Med Chem. 2009 Aug 13;52(15):4725-42. doi: 10.1021/jm9002654.

Abstract

The vascular cell adhesion molecule-1 (VCAM-1) has distinct roles in inflammatory cell recruitment to the damaged vessel wall. In the present work, a cyclic heptapeptide phage displayed library was screened in vitro during four rounds of biopanning. On the basis of Kd and IC50 values, a peptide (encoded as R832) was selected for in vitro and in vivo validation. After conjugation to Gd-DOTA, VCAM-1 imaging was assessed by MRI on a model of T cell mediated hepatitis, induced in mice by concanavalin A. On histological samples, the location of biotinylated R832 (R832-Bt) around liver veins in hepatitis resembles the pattern of MRI enhancement. Gd-DOTA-R832 was then assessed on ApoE(-/-) mice and produced an important signal enhancement of the aortic wall, while R832-Bt interacted with morphologic structures comparable to those marked by anti-VCAM-1 antibody. In conclusion, the in vitro and in vivo evaluation of peptide R832 suggests a specific interaction with the targeted biomolecule. Its conjugation to imaging reporters could assist the diagnosis of inflammatory diseases.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Apolipoproteins E / physiology
  • Cells, Cultured
  • Hepatitis / metabolism*
  • Heterocyclic Compounds
  • Humans
  • Integrin alpha4beta1 / metabolism
  • Integrin beta1 / metabolism
  • Magnetic Resonance Imaging / methods*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Organometallic Compounds
  • Peptide Library*
  • Vascular Cell Adhesion Molecule-1 / analysis*

Substances

  • Apolipoproteins E
  • Heterocyclic Compounds
  • Integrin alpha4beta1
  • Integrin beta1
  • Organometallic Compounds
  • Peptide Library
  • Vascular Cell Adhesion Molecule-1
  • gadolinium 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetate