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Archives of cardiovascular diseases
Volume 102, n° S1
page 17 (mars 2009)
Doi : 10.1016/S1875-2136(09)72163-1
Themes et posters

A030 In vivo molecular imaging of vascular cell adhesion molecule-1 expression in atherosclerotic plaques
 

J. Dimastromatteo 1, 2, 4, M. Ahmadi 1, 2, A. Broisat 1, 2, L.-M. Riou 1, 2, D. Boturyn 1, 3, M. Henri 1, 2, D. Garin 1, 2, G. Pons 1, 2, J. Tocsek 1, 2, P. Dumy 1, 3, D. Fagret 1, 2, C. Ghezzi 1, 2
1 Université Joseph Fourier, Grenoble, France 
2 Inserm U877, Grenoble, France 
3 UMR CNRS 5616, Grenoble, France 
4 ERAS Labo, Grenoble, France 

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Objectives

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.

Material and Methods

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.

Results

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).

Conclusion

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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