Abstract 3657: Cell-Specific Delivery and Monitoring of Antiangiogenic Therapy in Experimental Aortic Valve Disease with Theranostic Integrin-Targeted 19F Nanobeacons
Although angiogenesis plays a critical role in the development of atherosclerosis, its participation in early valvular disease remains speculative. To delineate the presence of angiogenesis and its potential responsiveness to medical therapy in experimental valve disease, we used unique signaling (19F), background-free molecular MR nanobeacons as simultaneous diagnostic and therapeutic (theranostic) tools to quantify valvular angiogenesis in 24 cholesterol-fed NZW rabbits (0.25% cholesterol, 6 mo.) and its response to nanoparticle-borne antiangiogenic therapy with an aminopeptidase-2 inhibitor, fumagillin. Perfluorocarbon nanobeacons (~250 nm) targeted to neovascular αvβ3 integrins and loaded with 0.2% fumagillin were given i.v. at 1 mL/kg for 4 weekly doses (n=8; 30 μg/kg fumagillin/dose). Controls included treatment with nontargeted drug-bearing nanoparticles (n=7) and saline (n=9). MR spectroscopy (470 MHz) for detection of 19F signal from bound nanoparticles was performed after valve excision. Immunocytochemistry confirmed angiogenesis in all valves. In the targeted drug treatment group, both 50% fewer vessels and 50% lower 19F signal were observed vs nontargeted or saline groups (p<0.01, p<0.001), confirming efficacy of the theranostic agent in limited dosing (Figure 1⇓). Across all animals, cholesterol levels exerted a strong linear effect on the extent of angiogenesis (r=0.52; p<0.01). We speculate that targeted therapy of angiogenesis with theranostic nanoparticles could offer an alternative or conjunctive approach for rational medical management of valvular disease.