Vascular Cell Adhesion Molecule-1 (VCAM-1) plays a major role in the chronic inflammatory processes involved in vulnerable atherosclerotic plaque development. It has been shown that the technetium-labelled HMC-I derived peptide B2702p bound specifically to VCAM-1 and allowed the ex vivo imaging of atherosclerotic lesions in WHHL rabbits. However, B2702p target-to-background ratio was suboptimal for in vivo imaging of VCAM-1 expression in atherosclerotic lesions. In order to increase the target to background ratio, ten derivatives of B2702p were synthesized (B2702p-1 to 10). We hypothesized that technetium radiolabelled B2702p derivatives might allow the molecular imaging of VCAM-1 expression in an experimental model of atherosclerosis.
A mouse model of focal atherosclerotic plaque development induced by left carotid artery ligation in ApoE-/- mice was used. 99mTc-B2702p (n=9) and 99mTc- B2702p-1 – 10 (n=3 for each except B2702p-1, n=5, and B2702p-4, n=5) were injected intravenously to the anesthetized animals 3 weeks following the ligation. Whole-body planar image acquisition was performed for 3 hrs with all radiolabelled peptides and SPECT imaging of 6 additionnal mice was also performed with 99mTc-B2702p-1. The animals were then euthanized and the biodistribution evaluated by gamma-well counting of excised organs. The expression of VCAM-1 in the ligated and contralateral arteries was evaluated by immunohistology.
A robust VCAM-1 immunostaining was observed in ApoE-/- mice in the atherosclerotic lesions at the level of the left carotid whereas no VCAM-1 expression was detected in the contralateral carotid. Among the ten evaluated peptides, 99mTc-B2702p-1 exhibited the more favourable properties. By gamma-well counting, there was a significant 2.0-fold increase in 99mTc-B2702p-1 left-to-right carotid artery activity ratio (2.61±0.61) and a 3.4-fold increase in left carotid-to-blood activity ratio (1.41±0.36) in comparison to 99mTc-B2702p (1.32±0.23 and 0.41±0.09, respectively, P<0.05 for both comparisons). Finally, a higher 99mTc-B2702p-1 activity in the left than in the right carotid was observed by SPECT imaging (33.3±5.8 vs. 25.1±5.3 cpm/mm2/ID, respectively, P<0.05).
Radiolabelled-B2702p-1 is a potentially useful radiotracer for the in vivo molecular imaging of VCAM-1 expression in atherosclerotic plaques.
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