Magnetic resonance molecular imaging of vascular cell adhesion molecule-1 expression in inflammatory lesions using a peptide-vectorized paramagnetic imaging probe.
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.
Burtea
Carmen
C
Department of General, Organic and Biomedical Chemistry, NMR and Molecular Imaging Laboratory, University of Mons, 24 Avenue du Champ de Mars, B-7000 Mons, Belgium.
Laurent
Sophie
S
Port
Marc
M
Lancelot
Eric
E
Ballet
Sébastien
S
Rousseaux
Olivier
O
Toubeau
Gérard
G
Vander Elst
Luce
L
Corot
Claire
C
Muller
Robert N
RN
D000595:Amino Acid Sequence; D000818:Animals; D001057:Apolipoproteins E / Q000502:physiology; D002478:Cells, Cultured; D006505:Hepatitis / Q000378:metabolism*; D006571:Heterocyclic Compounds; D006801:Humans; D039041:Integrin alpha4beta1 / Q000378:metabolism; D019012:Integrin beta1 / Q000378:metabolism; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009942:Organometallic Compounds; D019151:Peptide Library; D019010:Vascular Cell Adhesion Molecule-1 / Q000032:analysis*
D001057:Apolipoproteins E; D006571:Heterocyclic Compounds; D039041:Integrin alpha4beta1; D019012:Integrin beta1; D009942:Organometallic Compounds; D019151:Peptide Library; D019010:Vascular Cell Adhesion Molecule-1; C050823:gadolinium 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetate