Abstract 1723: In vivo Imaging of Anti-Atherosclerotic Pharmacotherapy with a VCAM-1 Targeted Multimodal Nanoparticle
Background: Vascular cell adhesion molecule-1 (VCAM-1) mediates recruitment of inflammatory cells into evolving atherosclerotic lesions. Here we tested the ability of VINP-28 (VCAM-1 Internalizing NanoParticle), a magnetofluorescent nanoparticle with a multimeric peptide affinity ligand identified from in vivo phage display, to monitor statin therapy in vivo.
Methods: 15 apoE−/− mice received a high-cholesterol diet (HCD, 0.2% total cholesterol) for 22 weeks. 8 mice received 8 weeks of HCD enriched with 0.01% w/w of atorvastatin. All animals received VINP-28 intravenously (30 mg Fe/kg). T2 weighted gradient echo images of the aortic root, a predominant region of atherosclerosis in this mouse model, were obtained on a 9.4 Tesla scanner with ECG and respiratory gating (TE, 4.7 ms; TR, 7.0 ms; in-plane resolution 0.125x0.125mm). Subsequently, aortas were excised for macroscopic fluorescence reflectance imaging (FRI), immunohistochemistry analysis and immunoblotting for VCAM-1 expression.
Results: In vivo MR and optical imaging revealed VINP-28 accumulation in the aortic root which correlated well (r2 =0.87, p =0.005) with VCAM-1 expression as assessed by immunohistochemistry. Atorvastatin-treated mice showed a lower contrast to noise ratio due to reduced VINP-28 deposition by in vivo MRI (Figure⇓, p =0.05). In FRI, the target to background ratio was lower in atorvastatin-treated mice. The finding of reduced VCAM-1 expression was corroborated by immunohistochemistry and immunoblotting.
Conclusion: VINP-28 allows noninvasive imaging of VCAM-1 expression in atherosclerosis and spatial monitoring of anti-atherosclerotic pharmacotherapy in vivo.