MR Angiogenesis Imaging with Robo4‐ versus α V β 3 ‐ Targeted Nanoparticles in the B16/F10 Mouse Melanoma Model

The objectives of the present study were: 1) to compare noninvasive MR molecular imaging utilizing Robo4 and α ν β 3 –integrin as biosignatures of angiogenesis, 2) to determine the relative spatial distribution of Robo4 and α ν β 3 within tumor neovessels, and 3) to assess the prevalence of angiogenesis in a mouse model implanted with a rapidly growing, syngeneic tumor. B16‐F10 melanoma bearing mice were imaged with MR (3.0T) 11 days post implantation after intravenous administration of Robo4‐, α ν β 3 –, irrelevant‐, or non‐targeted paramagnetic nanoparticles. Neovascular signal enhancement was predominantly associated with the tumor periphery where it was greater for α ν β 3 –integrin than Robo4 (p<0.05). The mean MR contrast enhancement in the tumor cores did not differ from zero in the α ν β 3 –, irrelevant‐, and non‐targeted groups and was similarly low, but greater than zero (p<0.006) in the Robo4 animals. Microscopic examination of tumors co‐exposed to the Robo4 and α ν β 3 –targeted nanoparticles corroborated the MR angiogenesis mapping results and further revealed that Robo4 expression generally colocalized with α ν β 3 – integrin. These results suggest that α ν β 3 –integrin and Robo4 are useful biomarkers for noninvasive MR molecular imaging in syngeneic mouse tumors.