An enzymatically activated fluorescence probe for targeted tumor imaging

被引:147
作者
Kamiya, Mako
Kobayashi, Hisataka
Hama, Yukihiro
Koyama, Yoshinori
Bernardo, Marcelino
Nagano, Tetsuo
Choyke, Peter L.
Urano, Yasuteru
机构
[1] NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA
[2] SAIC, Res Technol Program, Frederick, MD 21702 USA
[3] Japan Sci & Technol Agcy, PRESTO, Kawaguchi, Saitama 3320012, Japan
[4] Univ Tokyo, Grad Sch Pharmaceut Sci, Bunkyo Ku, Tokyo 1130033, Japan
关键词
D O I
10.1021/ja067710a
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
beta-Galactosidase is a widely used reporter enzyme, but although several substrates are available for in vitro detection, its application for in vivo optical imaging remains a challenge. To obtain a probe suitable for in vivo use, we modified our previously developed activatable fluorescence probe, TG-beta Gal (J. Am. Chem. Soc. 2005, 127, 4888-4894), on the basis of photochemical and photophysical experiments. The new probe, AM-TG-beta Gal, provides a dramatic fluorescence enhancement upon reaction with beta-galactosidase, and further hydrolysis of the ester moiety by ubiquitous intracellular esterases affords a hydrophilic product that is well retained within the cells without loss of fluorescence. We used a mouse tumor model to assess the practical utility of AM-TG-beta Gal, after confirming that tumors in the model could be labeled with an avidin-beta-galactosidase conjugate. This conjugate was administered to the mice in vivo, followed by AM-TG-beta Gal, and subsequent ex vivo fluorescence imaging clearly visualized intraperitoneal tumors as small as 200 mu m. This strategy has potential clinical application, for example, in video-assisted laparoscopic tumor resection.
引用
收藏
页码:3918 / 3929
页数:12
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