MR angiogenesis imaging with Robo4-vs. alpha(V)beta(3)-targeted nanoparticles in a B16/F10 mouse melanoma model

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

来源：The FASEB Journal, 2010, 24(11): 4262-4270.

DOI：10.1096/fj.10-157933

• magnetic resonance imaging
• integrin
• neovasculature
• roundabout
• tumor

The primary objective of this study was to utilize MR molecular imaging to compare the 3-dimensional spatial distribution of Robo4 and alpha(V)beta(3)-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 alpha(V)beta(3)-targeted paramagnetic nanoparticles. The percentage of MR signal-enhanced voxels throughout the tumor volume was low and increased in animals receiving alpha(V)beta(3)- 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 alpha(V)beta(3)-targeted nanoparticles corroborated the MR angiogenesis mapping results and further revealed that Robo4 expression generally colocalized with alpha(V)beta(3)-integrin. Robo4- and alpha(V)beta(3)-targeted nanoparticles were compared to irrelevant or nontargeted control groups in all modalities. These results suggest that alpha(V)beta(3)-integrin and Robo4 are useful biomarkers for noninvasive MR molecular imaging in syngeneic mouse tumors, but alpha(V)beta(3)-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 alpha(V)beta(3)-integrin expression, may help define tumor character prior to and following cancer therapy.-Boles, K. S., Schmieder, A. H., Koch, A. W., Carano, R. A. D., Wu, Y., Caruthers, S. D., Tong, R. K., Stawicki, S., Hu, G., Scott, M. J., Zhang, H., Reynolds, B. A., Wickline, S. A., and Lanza, G. M. MR angiogenesis imaging with Robo4- vs. alpha(V)beta(3)-targeted nanoparticles in a B16/F10 mouse melanoma model. FASEB J. 24, 4262-4270 (2010). www.fasebj.org

• 出版日期2010-11