Fluorescence lifetime Imaging system for in vivo studies

Fluorescence lifetime Imaging system for in vivo studies
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DOI:
10.2310/7290.2007.00019
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发表时间:
2007-07-01
期刊:
影响因子:
2.8
通讯作者:
Gandjbakhche, Amir H.
Gandjbakhche, Amir H.
中科院分区:
医学4区
文献类型:
--
作者:
Hassan, Moinuddin;Riley, Jason;Gandjbakhche, Amir H.

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本文介绍了一种小动物荧光寿命成像系统。通过用测量头扫描感兴趣区域来收集数据,测量头是在单个源光纤和几个检测光纤之间具有固定间隔的线性光纤阵列。其目标是使用特定的荧光标记物定位肿瘤并监测其进展。我们选择了近红外造影剂Alexa Fluor 750(加利福尼亚州卡尔斯巴德的Invitgen Corp.)。初步结果表明,这种染料的荧光寿命对荧光团的直接环境(特别是pH)很敏感,这使它成为报告荧光团周围生理变化的一个有前途的候选者。为了量化深度嵌入的荧光团的本征寿命,我们进行了体模实验,通过计算荧光强度衰减时间来研究光子迁移效应对观测寿命的贡献。以前提出的基于随机游走理论的迁移理论模型也被新的实验数据所证实。所开发的实验系统已用于与肿瘤特异性抗体(曲妥珠单抗[Herceptin])偶联的Alexa Fluor 750造影剂进行小鼠体内成像。荧光寿命的三维图谱表明,小鼠浅表性乳腺癌肿瘤的寿命值较低。
In this article, a fluorescence lifetime imaging system for small animals is presented. Data were collected by scanning a region of interest with a measurement head, a linear fiber array with fixed separations between a single source fiber and several detection fibers. The goal was to localize tumors and monitor their progression using specific fluorescent markers. We chose a near-infrared contrast agent, Alexa Fluor 750 (Invitrogen Corp., Carlsbad, CA). Preliminary results show that the fluorescence lifetime for this dye was sensitive to the immediate environment of the fluorophore (in particular, pH), making it a promising candidate for reporting physiologic changes around a fluorophore. To quantify the intrinsic lifetime of deeply embedded fluorophores, we performed phantom experiments to investigate the contribution of photon migration effects on observed lifetime by calculating the fluorescence intensity decay time. A previously proposed theoretical model of migration, based on random walk theory, is also substantiated by new experimental data. The developed experimental system has been used for in vivo mouse imaging with Alexa Fluor 750 contrast agent conjugated to tumor-specific antibodies (trastuzumab [Herceptin]). Three-dimensional mapping of the fluorescence lifetime indicates lower lifetime values in superficial breast cancer tumors in mice.