Molecular imaging of vascular cell adhesion molecule-1 expression in experimental atherosclerotic plaques with
A Broisat1, L M Riou, V Ardisson
1INSERM, U340, Radiopharmaceutiques Biocliniques, 38700, La Tronche, France.
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.
Insights
Radiolabeled B2702-p shows promise for imaging VCAM-1 in atherosclerosis. This tracer effectively visualizes VCAM-1 expression in atherosclerotic plaques, aiding in disease diagnosis and monitoring.
Area of Science:
- Cardiovascular Research
- Molecular Imaging
- Biomedical Engineering
Background:
- Vascular cell adhesion molecule-1 (VCAM-1) is crucial in chronic inflammation within atherosclerotic plaques.
- Specific peptide sequences (B2702-p and B2702-rp) from MHC-1 molecule B2702 bind to VCAM-1.
Purpose of the Study:
- To evaluate the potential of radiolabeled B2702-p and B2702-rp for molecular imaging of VCAM-1 in atherosclerosis.
- To assess the feasibility of using these tracers for detecting VCAM-1 expression in atherosclerotic lesions.
Main Methods:
- 123I- or 99mTc-labelled B2702-p was administered intravenously to hyperlipidemic rabbits (WHHL) and control animals.
- Aortas were analyzed ex vivo using autoradiography, gamma-well counting, and immunohistology for VCAM-1 and lipid staining.
Main Results:
- Significant increases in aortic-to-blood ratios for 123I-B2702-p and 99mTc-B2702-p were observed in WHHL rabbits compared to controls.
- Tracer uptake on ex vivo images correlated with atherosclerotic plaque locations and VCAM-1 expression levels.
- High tracer activity ratios were found in VCAM-1-positive areas of atherosclerotic plaques.
Conclusions:
- Radiolabeled B2702-p demonstrates potential as a valuable radiotracer for molecular imaging of VCAM-1 in atherosclerosis.
- This approach may facilitate non-invasive assessment of VCAM-1 expression in vulnerable atherosclerotic plaques.
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