Three-dimensional MR mapping of angiogenesis with α5β 1νβ3)-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, Gregory M. Lanza

Research output: Contribution to journalArticlepeer-review

116 Scopus citations

Abstract

Our objectives were 1) to characterize angiogenesis in the MDA-MB-435 xenograft mouse model with three-dimensional (3D) MR molecular imaging using α5β1(RGD)- or irrelevant RGS-targeted paramagnetic nanoparticles and 2) to use MR molecular imaging to assess the antiangiogenic effectiveness of α5β1νβ3)- vs. ανβ 3-targeted fumagillin (50 μg/kg) nanoparticles. Tumor-bearing mice were imaged with MR before and after administration of either α5β1(RGD) or irrelevant RGS-paramagnetic nanoparticles. In experiment 2, mice received saline or α 5β1νβ3)- or ανβ3-targeted fumagillin nanoparticles on days 7, 11, 15, and 19 posttumor implant. On day 22, MRI was performed using α5β1νβ3)- targeted paramagnetic nanoparticles to monitor the antiangiogenic response. 3D reconstructions of α5β1(RGD)-signal enhancement revealed a sparse, asymmetrical pattern of angiogenesis along the tumor periphery, which occupied <2.0% tumor surface area. α5β 1-targeted rhodamine nanoparticles colocalized with FITC-lectin corroborated the peripheral neovascular signal. α5β 1νβ3)-fumagillin nanoparticles decreased neovasculature to negligible levels relative to control; ανβ3-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.

Original languageEnglish
Pages (from-to)4179-4189
Number of pages11
JournalFASEB Journal
Volume22
Issue number12
DOIs
StatePublished - Dec 2008

Keywords

  • Antiangiogenic
  • Cancer
  • Fumagillin
  • Magnetic resonance imaging
  • Molecular imaging

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