99mTc-cAbVCAM1-5 Imaging Is a Sensitive and Reproducible Tool for the Detection of Inflamed Atherosclerotic Lesions in Mice: Sensitivity of 99mTc-cAbVCAM1-5 imaging

Abstract : 99mTc-cAbVCAM1-5 is a single-domain antibody fragment (sd-Ab) directed against mouse/human Vascular Cell Adhesion Molecule 1 (VCAM-1) which has recently been proposed as a new imaging agent for the detection of inflamed atherosclerotic lesions. Indeed, in a mouse model of atherosclerosis, 99mTc-cAbVCAM1-5 specifically bound to VCAM-1 positive lesions, thereby allowing their identification on SPECT images. The purpose of the present study was to investigate 99mTc-cAbVCAM1-5 imaging sensitivity using a reference statin therapy. Methods. Thirty ApoE-deficient mice were fed a western-type diet. First, the relationship between the level of VCAM-1 expression and 99mTc-cAbVCAM1-5 uptake was evaluated in 18 mice using immunohistochemistry and autoradiography (ARG). Second, longitudinal SPECT/CT imaging was performed on control (n=9) or atorvastatin-treated mice (0.01% w/w, n=9). Results. 99mTc-cAbVCAM1-5 uptake in atherosclerotic lesions correlated with the level of VCAM-1 expression (P<0.05). Atorvastatin exerted significant anti-atherogenic effects, and 99mTc-cAbVCAM1-5 lesion uptake was significantly reduced in 35 weeks-old atorvastatin-treated mice, as indicated by ex vivo gamma-well counting and ARG (p<0.05). Contrast-CT based SPECT imaging quantification was reproducible (inter experimenter ICC = 0.97, intra experimenter ICC = 0.90), and yielded results that were highly correlated with tracer biodistribution (r=0.83; P<0.0001). Therefore, reduced 99mTc-cAbVCAM1-5 uptake in atorvastatin-treated mice was successfully monitored non-invasively by SPECT/CT imaging (0.87 ± 0.06 %ID/cm3 vs 1.11 ± 0.09 %ID/cm3 in control group, P<0.05). Conclusions. 99mTc-cAbVCAM1-5 imaging allowed the specific, sensitive and reproducible quantification of VCAM-1 expression in mice atherosclerotic lesions. 99mTc-cAbVCAM1-5 therefore exhibits suitable characteristics for the evaluation of novel anti-atherogenic agents.
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European Journal of Nuclear Medicine, Springer-Verlag, 2014, 55 (10), pp.1678-1684. 〈10.2967/jnumed.114.143792〉
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Alexis Broisat, Jakub Toczek, Laurent Dumas, Mitra Ahmadi, Sandrine Bacot, et al.. 99mTc-cAbVCAM1-5 Imaging Is a Sensitive and Reproducible Tool for the Detection of Inflamed Atherosclerotic Lesions in Mice: Sensitivity of 99mTc-cAbVCAM1-5 imaging. European Journal of Nuclear Medicine, Springer-Verlag, 2014, 55 (10), pp.1678-1684. 〈10.2967/jnumed.114.143792〉. 〈inserm-01077899〉

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