MR angiogenesis imaging with Robo4- vs. α_Vβ ₃-targeted nanoparticles in a B16/F10 mouse melanoma model

The primary objective of this study was to utilize MR molecular imaging to compare the 3-dimensional spatial distribution of Robo4 and α _Vβ₃-integrin as biosignatures of angiogenesis, in a rapidly growing, syngeneic tumor. B16-F10 melanoma-bearing mice were imaged with magnetic resonance (MR; 3.0 T) 11 d postimplantation before and after intravenous administration of either Robo4- or α_Vβ ₃-targeted paramagnetic nanoparticles. The percentage of MR signalenhanced voxels throughout the tumor volume was low and increased in animals receiving α_Vβ₃- and Robo4-targeted nanoparticles. Neovascular signal enhancement was predominantly associated with the tumor periphery (i.e., outer 50% of volume). Microscopic examination of tumors coexposed to the Robo4- and α_Vβ₃- targeted nanoparticles corroborated the MR angiogenesis mapping results and further revealed that Robo4 expression generally colocalized with α_Vβ₃-integrin. Robo4- and α _Vβ₃--targeted nanoparticles were compared to irrelevant or nontargeted control groups in all modalities. These results suggest that α_Vβ₃-integrin and Robo4 are useful biomarkers for noninvasive MR molecular imaging in syngeneic mouse tumors, but α_Vβ₃-integrin expression was more detectable by MR at 3.0 T than Robo4. Noninvasive, neovascular assessments of the MR signal of Robo4, particularly combined with α_Vβ₃- integrin expression, may help define tumor character prior to and following cancer therapy.