Three‐dimensional MR mapping of angiogenesis with α 5 β 1 (α v β 3 )‐targeted theranostic nanoparticles in the MDA‐MB‐435 xenograft mouse model

Abstract

Our objectives were 1 ) to characterize angiogenesis in the MDA‐MB‐435 xenograft mouse model with three‐dimensional (3D) MR molecular im aging using α 5 β 1 (RGD)‐ or irrelevant RGS‐targeted paramagnetic nanoparticles and 2 ) to use MR molecu lar imaging to assess the antiangiogenic effectiveness of α 5 β 1 ( α v β 3 ) ‐ vs . α v β 3 ‐targeted fumagillin (50 μg/kg) nanoparticles. Tumor‐bearing mice were imaged with MR before and after administration of either α 5 β 1 (RGD) or irrelevant RGS‐paramagnetic nanopar ticles. In experiment 2, mice received saline or α 5 β 1 (α v β 3 )‐ or α v β 3 ‐targeted fumagillin nanoparticles on days 7, 11, 15, and 19 posttumor implant. On day 22, MRI was performed using α 5 β 1 (α v β 3 )‐targeted paramagnetic nanoparticles to monitor the antiangiogenic response. 3D reconstructions of α 5 β 1 (RGD)‐signal en hancement revealed a sparse, asymmetrical pattern of angiogenesis along the tumor periphery, which occupied <2.0% tumor surface area. α 5 β 1 ‐targeted rhodamine nanoparticles colocalized with FITC‐lectin corroborated the peripheral neovascular signal. α 5 β 1 (α v β 3 )‐fumagillin nanoparticles decreased neovas culature to negligible levels relative to control;α v β 3 ‐ targeted fumagillin nanoparticles were less effective ( P >0.05). Reduction of angiogenesis in MDA‐MB‐435 tumors from low to negligible levels did not decrease tumor volume. MR molecular imaging may be useful for characterizing tumors with sparse neovasculature that are unlikely to have a reduced growth response to targeted antiangiogenic therapy.— Schmieder, A. H., Caruthers, S. D., Zhang, H., Williams, T. A., Robertson, J. D., Wickline, S. A., Lanza, G. M. Three‐dimensional MR mapping of angiogenesis with α5β1(αvβ3)‐targeted theranostic nanoparticles in the MDA‐MB‐435 xenograft mouse model. FASEB J. 22, 4179–4189 (2008)