Whole-body fluorescence lifetime imaging of a tumor-targeted near-infrared molecular probe in mice
Whole-body fluorescence lifetime imaging of a tumor-targeted near-infrared molecular probe in mice
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DOI：
10.1117/1.2070148
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发表时间：
2005-09-01
影响因子：
3.5
通讯作者：
Achilefu, S
中科院分区：
文献类型：
--
作者：
Bloch, S;Lesage, F;Achilefu, S
荧光寿命成像可以提供与疾病功能状态相关的有价值的诊断信息。在这项研究中，合成了近红外（NIR）染料标记的六肽（缩写为Cyp-GRD）。在体外，Cyp-GRD 内化于非小细胞肺癌细胞 (A549) 中，浓度高达 1 X 10(-4) M 时，对细胞没有观察到细胞毒性或增殖作用。注射到 A549 荷瘤小鼠体内的 Cyp-GRD 的时域荧光强度和寿命成像表明，探针优先在肿瘤和主要排泄器官中积累。绘制了肿瘤部位缀合物的荧光寿命图，显示了与其环境相关的寿命的空间分布。此外，通过整合时间分辨强度获得的荧光强度图像重建能够显示不同深度切片中肿瘤与肾脏或肝脏的对比度。当对那些表现出足够信噪比的像素进行平均时，肿瘤的平均寿命为 1.03 ns，肝脏的平均寿命为 0.80 ns，这表明肿瘤具有更高的平均寿命，并反映了肿瘤病理生理学的改变。这项研究清楚地证明了全身近红外荧光寿命成像用于活体小动物肿瘤定位及其空间功能状态的可行性。 (c) 2005 年光电仪器工程师协会。
Fluorescence lifetime imaging can provide valuable diagnostic information relating to the functional status of diseases. In this study, a near-infrared (NIR) dye-labeled hexapeptide (abbreviated Cyp-GRD) was synthesized. In vitro, Cyp-GRD internalized in nonsmall cell lung cancer cells (A549) without observable cytotoxic or proliferative effects to the cells at a concentration up to 1 X 10(-4) M. Time-domain fluorescence intensity and lifetime imaging of Cyp-GRD injected into A549 tumor-bearing mice revealed that the probe preferentially accumulated in the tumor and the major excretion organs. The fluorescence lifetime of the conjugate at the tumor site was mapped, showing the spatial distribution of the lifetime related to its environment. Additionally, fluorescence intensity image reconstruction obtained by integrating the time-resolved intensities enabled the contrast ratios of tumor-to-kidney or liver in slices at different depths to be displayed. The mean lifetime was 1.03 ns for the tumor and 0.80 ns for the liver when averaging those pixels exhibiting adequate signal-to-noise ratio, showing the tumor had a higher lifetime average and reflecting the altered physiopathology of the tumor. This study clearly demonstrated the feasibility of whole-body NIR fluorescence lifetime imaging for tumor localization and its spatial functional status in living small animals. (c) 2005 Society of Photo-Optical Instrumentation Engineers.