Three-dimensional MR mapping of angiogenesis with α 5 β 1 (α ν β 3 )-targeted theranostic nanoparticles in the MDA-MB-435 xenograft mouse model Anne H. Schmieder * , Shelton D. Caruthers * ,† , Huiying Zhang * , Todd A. Williams * , J. David Robertson ‡ , Samuel A. Wickline * and Gregory M. Lanza * ,1 * Washington University Medical School, St. Louis, Missouri, USA; † Philips Healthcare, Andover, Massachusetts, USA; and ‡ University of Missouri Research Reactor, Columbia, Missouri, USA 1 Correspondence: Washington University Medical School, Campus Box 8215, 4320 Forest Park Ave., St. Louis, MO 63108, USA. E-mail: greg@cvu.wustl.edu Our objectives were 1 ) to characterize angiogenesis in the MDA-MB-435 xenograft mouse model with three-dimensional (3D) MR molecular imaging using α 5 β 1 (RGD)- or irrelevant RGS-targeted paramagnetic nanoparticles and 2 ) to use MR molecular imaging to assess the antiangiogenic effectiveness of α 5 β 1 (α ν β 3 )- vs. α ν 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 nanoparticles. In experiment 2, mice received saline or α 5 β 1 (α ν β 3 )- or α ν 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 ν β 3 )-targeted paramagnetic nanoparticles to monitor the antiangiogenic response. 3D reconstructions of α 5 β 1 (RGD)-signal enhancement 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 ν β 3 )-fumagillin nanoparticles decreased neovasculature to negligible levels relative to control; α ν 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 α 5 β 1 (α ν β 3 )-targeted theranostic nanoparticles in the MDA-MB-435 xenograft mouse model. Key Words: magnetic resonance imaging • fumagillin • cancer • molecular imaging • antiangiogenic
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Three-dimensional MR mapping of angiogenesis with α5β1(ανβ3)-targeted theranostic nanoparticles in the MDA-MB-435 xenograft mouse model
Schmieder, Anne H.; Caruthers, Shelton D.; Zhang, Huiying; Williams, Todd A.; Robertson, J. David; Wickline, Samuel A.; Lanza, Gregory M.
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, Volume 22 (12): 4179
Fed of American Socs for Experimental Biology – Dec 1, 2008
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