Molecular imaging of vascular cell adhesion molecule-1 expression in experimental atherosclerotic plaques with radiolabelled B2702-p.
OBJECTIVE
VCAM-1 plays a major role in the chronic inflammatory processes present in vulnerable atherosclerotic plaques. The residues 75-84 (B2702-p) and 84-75/75-84 (B2702-rp) of the major histocompatibility complex-1 (MHC-1) molecule B2702 were previously shown to bind specifically to VCAM-1. We hypothesised that radiolabelled B2702-p and B2702-rp might have potential for the molecular imaging of vascular cell adhesion molecule-1 (VCAM-1) expression in atherosclerotic plaques.


METHODS
Preliminary biodistribution studies indicated that 125I-B2702-rp was unsuitable for in vivo imaging owing to extremely high lung uptake. 123I- or 99mTc-labelled B2702-p was injected intravenously to Watanabe heritable hyperlipidaemic rabbits (WHHL, n=6) and control animals (n=6). After 180 min, aortas were harvested for ex vivo autoradiographic imaging, gamma-well counting, VCAM-1 immunohistology and Sudan IV lipid staining.


RESULTS
Robust VCAM-1 immunostaining was observed in Sudan IV-positive and to a lesser extent in Sudan IV-negative areas of WHHL animals, whereas no expression was detected in control animals. Significant 2.9-fold and 1.9-fold increases in 123I-B2702-p and 99mTc-B2702-p aortic-to-blood ratios, respectively, were observed between WHHL and control animals (p<0.05). Tracer uptake on ex vivo images co-localised with atherosclerotic plaques. Image quantification indicated a graded increase in 123I-B2702-p and 99mTc-B2702-p activities from control to Sudan IV-negative and to Sudan IV-positive areas, consistent with the observed pattern of VCAM-1 expression. Sudan IV-positive to control area tracer activity ratios were 17.0+/-9.0 and 5.9+/-1.8 for 123I-B2702-p and 99mTc-B2702-p, respectively.


CONCLUSIONS
Radiolabelled B2702-p is a potentially useful radiotracer for the molecular imaging of VCAM-1 in atherosclerosis.
Broisat
A
A
INSERM, U340, Radiopharmaceutiques Biocliniques, 38700, La Tronche, France.
Riou
L M
LM
Ardisson
V
V
Boturyn
D
D
Dumy
P
P
Fagret
D
D
Ghezzi
C
C
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000000981:diagnostic imaging / Q000378:metabolism; D050197:Atherosclerosis / Q000000981:diagnostic imaging* / Q000473:pathology*; D001345:Autoradiography / Q000379:methods; D001391:Azo Compounds / Q000494:pharmacology; D003952:Diagnostic Imaging / Q000379:methods; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D007249:Inflammation; D007457:Iodine Radioisotopes / Q000627:therapeutic use; D008285:Major Histocompatibility Complex; D010446:Peptide Fragments / Q000494:pharmacology*; D011817:Rabbits; D011877:Radionuclide Imaging; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis*
D000276:Adjuvants, Immunologic; D001391:Azo Compounds; D007457:Iodine Radioisotopes; D010446:Peptide Fragments; D019010:Vascular Cell Adhesion Molecule-1; C118185:decapeptide B 2702; C009213:Scarlet Red