Magnetic Resonance Molecular Imaging of Vascular Cell Adhesion Molecule-1 Expression inInflammatory Lesions Using a Peptide-Vectorized Paramagnetic Imaging Probe

摘要

The vascular cell adhesion molecule-1 (VCAM-1) has distinct roles in inflammatory cell recruitment tothe damaged vessel wall. In the present work, a cyclic heptapeptide phage displayed library was screenedin vitro during four rounds of biopanning. On the basis of Kd and IC50 values, a peptide (encoded asR832) was selected for in vitro and in vivo validation. After conjugation to Gd-DOTA, VCAM- Iimaging was assessed by MRI on a model of T cell mediated hepatitis, induced in mice by concanavalinA. On histological samples, the location of biotinylated R832 (R832-Bt) around liver veins in hepatitisresembles the pattern of MRI enhancement. Gd-DOTA-R832 was then assessed on ApoE-/- mice andproduced an important signal enhancement of the aortic wall, while R832-Bt interacted withmorphologic structures comparable to those marked by anti-VCAM-1 antibody. In conclusion, thein vitro and in vivo evaluation of peptide R832 suggests a specific interaction with the targetedbiomolecule. Its conjugation to imaging reporters could assist the diagnosis of inflammatory diseases.