MR angiogenesis imaging with Robo4- vs. αVβ 3-targeted nanoparticles in a B16/F10 mouse melanoma model

Kent S. Boles, Anne H. Schmieder, Alexander W. Koch, Richard A.D. Carano, Yan Wu, Shelton D. Caruthers, Raymond K. Tong, Scott Stawicki, Grace Hu, Michael J. Scott, Huiying Zhang, Benton A. Reynolds, Samuel A. Wickline, Gregory M. Lanza

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

Abstract

The primary objective of this study was to utilize MR molecular imaging to compare the 3-dimensional spatial distribution of Robo4 and α Vβ3-integrin as biosignatures of angiogenesis, in a rapidly growing, syngeneic tumor. B16-F10 melanoma-bearing mice were imaged with magnetic resonance (MR; 3.0 T) 11 d postimplantation before and after intravenous administration of either Robo4- or αVβ 3-targeted paramagnetic nanoparticles. The percentage of MR signalenhanced voxels throughout the tumor volume was low and increased in animals receiving αVβ3- and Robo4-targeted nanoparticles. Neovascular signal enhancement was predominantly associated with the tumor periphery (i.e., outer 50% of volume). Microscopic examination of tumors coexposed to the Robo4- and αVβ3- targeted nanoparticles corroborated the MR angiogenesis mapping results and further revealed that Robo4 expression generally colocalized with αVβ3-integrin. Robo4- and α Vβ3--targeted nanoparticles were compared to irrelevant or nontargeted control groups in all modalities. These results suggest that αVβ3-integrin and Robo4 are useful biomarkers for noninvasive MR molecular imaging in syngeneic mouse tumors, but αVβ3-integrin expression was more detectable by MR at 3.0 T than Robo4. Noninvasive, neovascular assessments of the MR signal of Robo4, particularly combined with αVβ3- integrin expression, may help define tumor character prior to and following cancer therapy.

Original languageEnglish
Pages (from-to)4262-4270
Number of pages9
JournalFASEB Journal
Volume24
Issue number11
DOIs
StatePublished - Nov 2010

Keywords

  • Integrin
  • Magnetic resonance imaging
  • Neovasculature
  • Roundabout
  • Tumor

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