Molecular MR imaging of neovascular progression in the vx2 tumor with α_vβ₃-targeted paramagnetic nanoparticles

Purpose: To assess the dependence of neovascular molecular magnetic resonance (MR) imaging on relaxivity (r1) of avb3- targeted paramagnetic perfluorocarbon (PFC) nanoparticles and to delineate the temporal-spatial consistency of angiogenesis assessments for individual animals. Materials and Methods: Animal protocols were approved by the Washington University Animal Studies Committee. Proton longitudinal and transverse relaxation rates of avb3-targeted and nontargeted PFC nanoparticles incorporating gadolinium diethylenetrianime pentaacedic acid (Gd-DTPA) bisoleate (BOA) or gadolinium tetraazacyclododecane tetraacetic acid (Gd-DOTA) phosphatidylethanolamine (PE) into the surfactant were measured at 3.0 T. These paramagnetic nanoparticles were compared in 30 New Zealand White rabbits (four to six rabbits per group) 14 days after implantation of a Vx2 tumor. Subsequently, serial MR (3.0 T) neovascular maps were developed 8, 14, and 1±days after tumor implantation by using avb3-targeted Gd-DOTA- PE nanoparticles (n = 4) or nontargeted Gd-DOTA-PE nanoparticles (n = 4). Data were analyzed with analysis of variance and nonparametric statistics. Results: At 3.0 T, Gd-DTPA-BOA nanoparticles had an ionic r1 of 10.3 L · mmol21 · sec21 and a particulate r1 of 927 000 L · mmol21 · sec21. Gd-DOTA-PE nanoparticles had an ionic r1 of 13.3 L · mmol21 · sec21 and a particulate r1 of 1 197 000 L · mmol21 · sec21. Neovascular contrast enhancement in Vx2 tumors (at 14 days) was 5.4% ±1.0±of the surface volume with avb3-targeted Gd-DOTA- PE nanoparticles and 3.0% ±0.3 with avb3-targeted Gd-DTPA-BOA nanoparticles (P = .03). MR neovascular contrast maps of tumors 8, 14, and 1±days after implantation revealed temporally consistent and progressive surface enhancement (1.0% ±0.3, 4.5% ±0.9, and 9.3% ±1.4, respectively; P = .0008), with similar time-dependent changes observed among individual animals. Conclusion: Temporal-spatial patterns of angiogenesis for individual animals were followed to monitor longitudinal tumor progression. Neovasculature enhancement was dependent on the relaxivity of the targeted agent.