MR angiogenesis imaging with Robo4-vs. αVβ3-targeted nanoparticles in a B16/F10 mouse melanoma model
MR angiogenesis imaging with Robo4-vs. αVβ3-targeted nanoparticles in a B16/F10 mouse melanoma model
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DOI：
10.1096/fj.10-157933
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发表时间：
2010-11-01
期刊：
影响因子：
4.8
通讯作者：
Lanza, Gregory M.
中科院分区：
文献类型：
--
作者：
Boles, Kent S.;Schmieder, Anne H.;Lanza, Gregory M.
本研究的主要目的是利用MR分子成像比较快速生长的同源肿瘤中Robo 4和α（V）β（3）-整联蛋白作为血管生成生物特征的三维空间分布。在植入后11天，在静脉内给予Robo 4或α（V）β（3）靶向顺磁性纳米颗粒之前和之后，对携带B16-F10黑色素瘤的小鼠进行磁共振（MR; 3.0 T）成像。整个肿瘤体积中MR信号增强体素的百分比较低，并且在接受α（V）β（3）和Robo 4靶向纳米颗粒的动物中增加。新生血管信号增强主要与肿瘤周边相关（即，体积的50%）。对共暴露于Robo 4和α（V）β（3）靶向纳米颗粒的肿瘤的显微镜检查证实了MR血管生成映射结果，并进一步揭示了Robo 4表达通常与α（V）β（3）整合素共定位。Robo 4-和alpha（V）beta（3）-靶向纳米颗粒在所有模式中与不相关或非靶向对照组进行比较。这些结果表明，α（V）β（3）-整联蛋白和Robo 4是同基因小鼠肿瘤中非侵入性MR分子成像的有用生物标志物，但在3.0 T下MR比Robo 4更能检测到α（V）β（3）-整联蛋白表达。Robo 4的MR信号的非侵入性新生血管评估，特别是与α（V）β（3）-整合素表达相结合，可能有助于在癌症治疗之前和之后确定肿瘤特征。Boles，K.美国，Schmieder，A. H、科赫，A. W.，卡拉诺河A. D、吴，Y.，卡鲁瑟斯，S. D、通河，巴西-地K.，斯塔维奇，S.，Hu，G.，斯科特，M。J.，张洪，雷诺兹，B。一、Wickline，S.一、和Lanza，G. M.在B16/F10小鼠黑色素瘤模型中使用Robo 4与alpha（V）beta（3）靶向纳米颗粒的MR血管生成成像。FASEB J.24，4262-4270（2010）。www.fasebj.org
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