PT - JOURNAL ARTICLE AU - Dimastromatteo, Julien AU - Broisat, Alexis AU - Perret, Pascale AU - Ahmadi, Mitra AU - Boturyn, Didier AU - Dumy, Pascal AU - Fagret, Daniel AU - Riou, Laurent M. AU - Ghezzi, Catherine TI - In Vivo Molecular Imaging of Atherosclerotic Lesions in ApoE<sup>−/−</sup> Mice Using VCAM-1–Specific, <sup>99m</sup>Tc-Labeled Peptidic Sequences AID - 10.2967/jnumed.112.115675 DP - 2013 Aug 01 TA - Journal of Nuclear Medicine PG - 1442--1449 VI - 54 IP - 8 4099 - http://jnm.snmjournals.org/content/54/8/1442.short 4100 - http://jnm.snmjournals.org/content/54/8/1442.full SO - J Nucl Med2013 Aug 01; 54 AB - Vascular cell adhesion molecule 1 (VCAM-1) plays a major role in the chronic inflammatory processes involved in vulnerable atherosclerotic plaque development. We previously showed that the 99mTc-labeled major histocompatibility complex 1–derived peptide B2702p bound specifically to VCAM-1 and allowed the ex vivo imaging of atherosclerotic lesions in Watanabe heritable hyperlipidemic rabbits. However, B2702p target-to-background ratio was suboptimal for the in vivo imaging of VCAM-1 expression in atherosclerotic lesions. To improve the target-to-background ratio, 20 derivatives of B2702p (B2702p1–B2702p20) were synthesized using the alanine scan methodology. We hypothesized that 99mTc-radiolabeled B2702p derivatives might allow the molecular imaging of VCAM-1 expression in an experimental model of atherosclerosis. Methods: A mouse model of focal atherosclerotic plaque development induced by left carotid artery ligation in apolipoprotein E double-knockout (ApoE−/−) mice was used (n = 82). 99mTc-B2702p and 99mTc-B2702p1–99mTc-B2702p20 were injected intravenously in anesthetized animals 3 wk after the ligation. Whole-body planar imaging was performed for 3 h. SPECT imaging of 6 additional ligated ApoE−/− mice was also performed with 99mTc-B2702p1. The animals were then euthanized, and the biodistribution of 99mTc-labeled peptides was evaluated by γ-well counting of excised organs. Expression of VCAM-1 in the ligated and contralateral carotid arteries was evaluated by immunohistology. Results: Robust VCAM-1 immunostaining was observed in the left carotid atherosclerotic lesions as a consequence of artery ligation, whereas no VCAM-1 expression was detected in the contralateral carotid artery. Among all evaluated peptides, 99mTc-B2702p1 exhibited the most favorable properties. By γ-well counting, there was a significant 2.0-fold increase in the 99mTc-B2702p1 left-to-right carotid artery activity ratio (2.6 ± 0.6) and a 3.4-fold increase in the left carotid-to-blood activity ratio (1.4 ± 0.4) in comparison to 99mTc-B2702p (1.3 ± 0.2 and 0.4 ± 0.1, respectively, P &lt; 0.05 for both comparisons). Similarly, planar image quantification indicated a higher left-to-right carotid activity ratio in 99mTc-B2702p1– than in 99mTc-B2702p–injected mice (1.2 ± 0.1 vs. 1.0 ± 0.0, respectively, P &lt; 0.05). Finally, a significantly higher 99mTc-B2702p1 activity in the left than in the right carotid artery was observed by SPECT imaging (2.2 ± 0.4 vs. 1.4 ± 0.3 cpm/mm2/injected dose, respectively, P &lt; 0.05). Conclusion: 99mTc-B2702p1 is a potentially useful radiotracer for the in vivo molecular imaging of VCAM-1 expression in atherosclerotic plaques.