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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Acknowledgements
Financial support was provided by the National Institute for Health and Medical Research (INSERM) and the French Ministry of National Education and Research. All the experimental protocols described in the present study were approved by the Animal Care and Use Committee of the Centre de Recherche et Service de Santé des Armées (CRSSA) and the experiments were performed by an authorised individual (A. Broisat, authorisation # 38 04 37).
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Broisat, A., Riou, L.M., Ardisson, V. et al. Molecular imaging of vascular cell adhesion molecule-1 expression in experimental atherosclerotic plaques with radiolabelled B2702-p. Eur J Nucl Med Mol Imaging 34, 830–840 (2007). https://doi.org/10.1007/s00259-006-0310-4
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DOI: https://doi.org/10.1007/s00259-006-0310-4