Molecular imaging of vascular cell adhesion molecule-1 expression in experimental atherosclerotic plaques with radiolabelled B2702-p | springermedicine.com

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European Journal of Nuclear Medicine and Molecular Imaging

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01-06-2007 | Molecular Imaging

Molecular imaging of vascular cell adhesion molecule-1 expression in experimental atherosclerotic plaques with radiolabelled B2702-p

Authors: A. Broisat, L. M. Riou, V. Ardisson, D. Boturyn, P. Dumy, D. Fagret, C. Ghezzi

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 6/2007

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Abstract

Purpose

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.

Conclusion

Radiolabelled B2702-p is a potentially useful radiotracer for the molecular imaging of VCAM-1 in atherosclerosis.

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Title: Molecular imaging of vascular cell adhesion molecule-1 expression in experimental atherosclerotic plaques with radiolabelled B2702-p
Authors: A. Broisat
L. M. Riou
V. Ardisson
D. Boturyn
P. Dumy
D. Fagret
C. Ghezzi
Publication date: 01-06-2007
Publisher: Springer-Verlag
Published in: European Journal of Nuclear Medicine and Molecular Imaging / Issue 6/2007
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-006-0310-4

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