HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Free Full Text (PDF) Free All Versions of this Article: fj.08-112060v1 22/12/4179    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Schmieder, A. H. Articles by Lanza, G. M. Search for Related Content PubMed PubMed Citation Articles by Schmieder, A. H. Articles by Lanza, G. M.

Three-dimensional MR mapping of angiogenesis with ₅β₁(β₃)-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

¹Correspondence: Washington University Medical School, Campus Box 8215, 4320 Forest Park Ave., St. Louis, MO 63108, USA. E-mail: greg{at}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 ₅β₁(RGD)- or irrelevant RGS-targeted paramagnetic nanoparticles and 2) to use MR molecular imaging to assess the antiangiogenic effectiveness of ₅β₁(β₃)- vs. β₃-targeted fumagillin (50 µg/kg) nanoparticles. Tumor-bearing mice were imaged with MR before and after administration of either ₅β₁(RGD) or irrelevant RGS-paramagnetic nanoparticles. In experiment 2, mice received saline or ₅β₁(β₃)- or β₃-targeted fumagillin nanoparticles on days 7, 11, 15, and 19 posttumor implant. On day 22, MRI was performed using ₅β₁(β₃)-targeted paramagnetic nanoparticles to monitor the antiangiogenic response. 3D reconstructions of ₅β₁(RGD)-signal enhancement revealed a sparse, asymmetrical pattern of angiogenesis along the tumor periphery, which occupied <2.0% tumor surface area. ₅β₁-targeted rhodamine nanoparticles colocalized with FITC-lectin corroborated the peripheral neovascular signal. ₅β₁(β₃)-fumagillin nanoparticles decreased neovasculature to negligible levels relative to control; β₃-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 ₅β₁(β₃)-targeted theranostic nanoparticles in the MDA-MB-435 xenograft mouse model.

Key Words: magnetic resonance imaging • fumagillin • cancer • molecular imaging • antiangiogenic

This article has been cited by other articles:

				R. F. Minchin and D. J. Martin Nanoparticles for Molecular Imaging--An Overview Endocrinology, February 1, 2010; 151(2): 474 - 481. [Abstract] [Full Text] [PDF]

				F. A. Jaffer, P. Libby, and R. Weissleder Optical and Multimodality Molecular Imaging: Insights Into Atherosclerosis Arterioscler Thromb Vasc Biol, July 1, 2009; 29(7): 1017 - 1024. [Abstract] [Full Text] [PDF]