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用于实体瘤异种移植成像的具有荧光和磁性特性的双探针。

Dual probe with fluorescent and magnetic properties for imaging solid tumor xenografts.

作者信息

Shan Liang, Wang Songping, Sridhar Rajagopalan, Bhujwalla Zaver M, Wang Paul C

机构信息

Department of Radiology and Radiation Oncology, Howard University, Washingron, DC 20060, USA.

出版信息

Mol Imaging. 2007 Mar-Apr;6(2):85-95.

Abstract

A dual probe with fluorescent and magnetic reporter groups was constructed by linkage of the near-infrared (NIR) fluorescent transferrin conjugate (Tf(NIR)) on the surface of contrast agent-encapsulated cationic liposome (Lip-CA). This probe was used for magnetic resonance imaging (MRI) and optical imaging of MDA-MB-231-luc breast cancer cells grown as a monolayer in vitro and as solid tumor xenografts in nude mice. Confocal microscopy, optical imaging, and MRI showed a dramatic increase of in vitro cellular uptake of the fluorescent and magnetic reporter groups from the probe compared with the uptake of contrast agent or Lip-CA alone. Pretreatment with transferrin (Tf) blocked uptake of the probe reporters, indicating the importance and specificity of the Tf moiety for targeting. Intravenous administration of the dual probe to nude mice significantly enhanced the tumor contrast in MRI, and preferential accumulation of the fluorescent signal was clearly seen in NIR-based optical images. More interestingly, the contrast enhancement in MRI showed a heterogeneous pattern within tumors, which reflected the tumor's morphologic heterogeneity. These results indicate that the newly developed dual probe enhances the tumor image contrast and is superior to contrast agent alone for identifying the tumor pathologic features on the basis of MRI but also is suitable for NIR-based optical imaging.

摘要

通过将近红外(NIR)荧光转铁蛋白缀合物(Tf(NIR))连接在包裹造影剂的阳离子脂质体(Lip-CA)表面,构建了一种具有荧光和磁性报告基团的双功能探针。该探针用于体外单层培养的MDA-MB-231-luc乳腺癌细胞以及裸鼠体内实体瘤异种移植瘤的磁共振成像(MRI)和光学成像。共聚焦显微镜、光学成像和MRI结果显示,与单独摄取造影剂或Lip-CA相比,探针中荧光和磁性报告基团的体外细胞摄取量显著增加。用转铁蛋白(Tf)预处理可阻断探针报告基团的摄取,表明Tf部分在靶向方面的重要性和特异性。将双功能探针静脉注射到裸鼠体内可显著增强MRI中的肿瘤对比度,并且在基于近红外的光学图像中清晰可见荧光信号的优先积累。更有趣的是,MRI中的对比度增强在肿瘤内呈现出异质性模式,这反映了肿瘤的形态学异质性。这些结果表明,新开发的双功能探针增强了肿瘤图像对比度,在基于MRI识别肿瘤病理特征方面优于单独的造影剂,并且也适用于基于近红外的光学成像。

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