Imaging of neovascularization in atherosclerotic plaque with 99mTc-labeled single chain VEGF: Proof of concept for imaging vulnerable plaque

Abstract

564

Objectives: Adventitial vasa vasorum proliferation and neointimal neovascularization are associated with intraplaque hemorrhage, expansion of necrotic core and hence plaque vulnerability. Increased expression of VEGF and its receptors accompany neoangiogenic process. We used Tc-99m labeled single chain VEGF (TcV) for developing potentially noninvasive imaging modality and compared it with Tc-99m labeled RGD probe targeting αvβ3 integrin (TcAB) within neovasculature. Methods: Noninvasive radionuclide imaging was performed with either TcV (6.85±0.27mCi) or TcAB (7.02±0.07mCi) in 12 NZW rabbits receiving high cholesterol diet (0.2% cholesterol, 4% fat) for one year and compared with 5 control rabbits receiving normal rabbit chow. Four hours after intravenous administration of TcV or TcAB, micro SPECT/microCT imaging was performed for in vivo localization of tracer activity. Aortas were then explanted, and gamma counted for determination of % injected dose per gram (%ID/g). The aortas were then submitted for histopathologic characterization. Results: Uptake in thoracic aorta was clearly visualized non-invasively both by TcV and TcAB in vivo imaging in 6 of 9 rabbits in hypercholesterolemic rabbits, but not in the control animals. The % ID/g of aortic arch in hypercholesterolemic rabbits (0.032±0.021%) was higher than that in control group (0.014±0.004%) in TcV group. The uptake of TcAB in hypercholesterolemic rabbits (0.039±0.015%) was also higher than that in control group (0.028±0.001%). Conclusions: This preliminary study suggests a potentially novel strategy for non-invasive imaging of neoangiogenesis in atherosclerotic plaque and may allow identification of unstable plaques.