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首页 » 癌症研究 » Neurosurgery:脑肿瘤细胞“亮”起来—新型荧光染料或能帮助定位脑肿瘤细胞

Neurosurgery:脑肿瘤细胞“亮”起来—新型荧光染料或能帮助定位脑肿瘤细胞

来源:生物谷 2015-02-02 15:21

2015年2月2日讯 /生物谷BIOON/ -- 美国威斯康辛大学临床和公共健康学院(University of Wisconsin School of Medicine and Public Health)的几名神经外科医生自主研发并实验了两种新型荧光染料。这两种染料能特异性附着在肿瘤细胞上,帮助神经外科医生更准确定位并完全切除脑瘤。这篇研究将发表在Neurosurgery杂志2月刊。

这两种荧光染料被命名为CLR1501和CLR1502。它们是肿瘤靶向剂alkylphosphocholine(APC)的合成类似物,能专门吸附到癌细胞。在特定波长的光照下(绿光-CLR1501,近红外-CLR1502),这两种染料就会发出荧光。

其实市面还有另外一种染料可用于脑肿瘤定位,名为5-氨基乙酰丙酸(5-ALA),在蓝光照射下发光。不过5-ALA主要应用在欧洲神经外科手术,在美国未被批准。于是威斯康辛大学的研究人员便自主研发可用的荧光染料。

在验证过程中,CLR1501,CLR1502,和5-ALA被注射到患有胶质细胞瘤和胶质母细胞瘤的小鼠身上,然后通过激光共聚焦显微镜,IVIS光谱成像系统或者近红外荧光的成像系统检测小鼠的脑组织。结果发现CLR1501的荧光效果与5-ALA染料相似。而近红外的CLR1502染料的荧光效果比5-ALA更好。

这一发现表明APC类似物可以应用在指导脑癌手术-有助于神经外科医生定位肿瘤,并尽可能完全切除它。而且在初步研究中发现,医生可以透过小鼠完整的皮肤和颅骨,直接近红外显色的CLR1502定位的脑肿瘤。除了引导神经外科手术,APC类似物将可能在脑肿瘤诊断和直接评价针对肿瘤的化疗药物效果起到有益的作用。(生物谷Bioon.com)

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DOI: 10.1227/NEU.0000000000000622

Fluorescent Cancer-Selective Alkylphosphocholine Analogs for Intraoperative Glioma Detection
Kyle I. Swanson, Paul A. Clark, Ray R. Zhang, Irawati K. Kandela, Mohammed Farhoud, Jamey P. Weichert, John S. Kuo

Abstract
BACKGROUND: 5-Aminolevulinic acid (5-ALA)-induced tumor fluorescence aids brain tumor resections but is not approved for routine use in the United States. We developed and describe testing of 2 novel fluorescent, cancer-selective alkylphosphocholine analogs, CLR1501 (green) and CLR1502 (near infrared), in a proof-of-principle study for fluorescence-guided glioma surgery.

OBJECTIVE: To demonstrate that CLR1501 and CLR1502 are cancer cell-selective fluorescence agents in glioblastoma models and to compare tumor-to-normal brain (T:N) fluorescence ratios with 5-ALA.

METHODS: CLR1501, CLR1502, and 5-ALA were administered to mice with magnetic resonance imaging-verified orthotopic U251 glioblastoma multiforme- and glioblastoma stem cell-derived xenografts. Harvested brains were imaged with confocal microscopy (CLR1501), the IVIS Spectrum imaging system (CLR1501, CLR1502, and 5-ALA), or the Fluobeam near-infrared fluorescence imaging system (CLR1502). Imaging and quantitative analysis of T:N fluorescence ratios were performed.

RESULTS: Excitation/emission peaks are 500/517 nm for CLR1501 and 760/778 nm for CLR1502. The observed T:N ratio for CLR1502 (9.28 ± 1.08) was significantly higher (P < .01) than for CLR1501 (3.51 ± 0.44 on confocal imaging; 7.23 ± 1.63 on IVIS imaging) and 5-ALA (4.81 ± 0.92). Near-infrared Fluobeam CLR1502 imaging in a mouse xenograft model demonstrated high- contrast tumor visualization compatible with surgical applications.

CONCLUSION: CLR1501 (green) and CLR1502 (near infrared) are novel tumor-selective fluorescent agents for discriminating tumor from normal brain. CLR1501 exhibits a tumor-to-brain fluorescence ratio similar to that of 5-ALA, whereas CLR1502 has a superior tumor-to-brain fluorescence ratio. This study demonstrates the potential use of CLR1501 and CLR1502 in fluorescence-guided tumor surgery.

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