Optical imaging of targeted β-galactosidase in brain tumors to detect EGFR levels.
Optical imaging of targeted β-galactosidase in brain tumors to detect EGFR levels.
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DOI：
10.1021/bc500597y
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发表时间：
2015-04-15
影响因子：
4.7
通讯作者：
Basilion, James
中科院分区：
文献类型：
--
作者：
Broome, Ann-Marie;Ramarnurthy, Gopal;Lavik, Kari;Liggett, Alexander;Kinstlinger, Ian;Basilion, James
目前分子成像的一个局限性是，它通常需要对癌细胞进行基因操作才能进行非侵入性成像。使用外源递送和功能活跃的报告程序(如β-GAL)检测体内肿瘤细胞的其他方法也是必需的。我们报道了一种平台系统的开发，用于将β-GAL连接到任何数量的不同配体或抗体，以便在体内靶向组织或细胞，而不需要在成像之前对目标细胞进行基因工程。我们的研究表明，在体外和体内，以表皮生长因子受体为靶点的β-GAL复合体具有显著的摄取作用。然后，我们能够成像原位脑瘤积聚和靶向酶的定位，以及在体外验证静脉注射β-GAL报告复合体的内化。在荧光成像将β-GAL复合体定位到脑瘤后，我们将生物发光的β-GAL底物局部应用于大脑的连续切片，以评估酶的传递和完整性。最后，在非侵入性体内成像过程中，肿瘤内捕捉到了以表皮生长因子受体为靶标的β-GAL复合体的强健生物发光。
A current limitation in molecular imaging is that it often requires genetic manipulation of cancer cells for noninvasive imaging. Other methods to detect tumor cells in vivo using exogenously delivered and functionally active reporters, such as β-gal, are required. We report the development of a platform system for linking β-gal to any number of different ligands or antibodies for in vivo targeting to tissue or cells, without the requirement for genetic engineering of the target cells prior to imaging. Our studies demonstrate significant uptake in vitro and in vivo of an EGFR-targeted β-gal complex. We were then able to image orthotopic brain tumor accumulation and localization of the targeted enzyme when a fluorophore was added to the complex, as well as validate the internalization of the intravenously administered β-gal reporter complex ex vivo. After fluorescence imaging localized the β-gal complexes to the brain tumor, we topically applied a bioluminescent β-gal substrate to serial sections of the brain to evaluate the delivery and integrity of the enzyme. Finally, robust bioluminescence of the EGFR-targeted β-gal complex was captured within the tumor during noninvasive in vivo imaging.
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影响因子：
5.2
作者：
Querol, M;Chen, JW;Bogdanov, A
通讯作者：
Bogdanov, A
影响因子：
5.7
作者：
Agnes RS;Broome AM;Wang J;Verma A;Lavik K;Basilion JP
通讯作者：
Basilion JP
DOI：
10.1073/pnas.0803945105
发表时间：
2008-11-25
影响因子：
11.1
作者：
Breckwoldt, Michael O.;Chen, John W.;Weissleder, Ralph
通讯作者：
Weissleder, Ralph
影响因子：
4.6
作者：
Chen, Shih-Hsien;Kuo, Yu-Ting;Wang, Yun-Ming
通讯作者：
Wang, Yun-Ming
DOI：
10.1007/978-3-319-12048-5_2
发表时间：
2015-01-01
期刊：
CURRENT UNDERSTANDING AND TREATMENT OF GLIOMAS
影响因子：
--
作者：
Cohen, Adam L.;Colman, Howard
通讯作者：
Colman, Howard