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- Title
Three-dimensional MR mapping of angiogenesis with α<sub>5</sub>β<sub>1</sub>(α<sub>v</sub>β<sub>3</sub>)-targeted theranostic nanoparticles in the MDA-MB-435 xenograft mouse model.
- Authors
Schmieder, Anne H.; Caruthers, Shelton D.; Huiying Zhang; Williams, Todd A.; Robertson, J. David; Wickline, Samuel A.; Lanza, Gregory M.
- 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 α5β1(αvβ3) - vs. αvβ3- 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 α5β5(αvβ3)- or αvβ3-targeted fumagillin nanoparticles on days 7, 11, 15, and 19 posttumor implant. On day 22, MRI was performed using α5β1(αvβ3)-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. α5β1-targeted rhodamine nanoparticles colocalized with FITC-lectin corroborated the peripheral neovascular signal. α5β1(αvβ3)-fumagillin nanoparticles decreased neovasculature to negligible levels relative to control; αvβ3 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.
- Subjects
MAGNETIC resonance imaging; NEOVASCULARIZATION; NANOPARTICLES; XENOGRAFTS; TUMORS; LABORATORY mice; RHODAMINE B
- Publication
FASEB Journal, 2008, Vol 22, Issue 12, p4179
- ISSN
0892-6638
- Publication type
Article
- DOI
10.1096/fj.08-112060