Bloch Sharon, Lesage Frédéric, McIntosh Laura, Gandjbakhche Amir, Liang Kexian, Achilefu Samuel
Washington University School of Medicine, Department of Radiology, St. Louis, Missouri 63110, USA.
J Biomed Opt. 2005 Sep-Oct;10(5):054003. doi: 10.1117/1.2070148.
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 1x10(-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.
荧光寿命成像能够提供与疾病功能状态相关的有价值的诊断信息。在本研究中，合成了一种近红外（NIR）染料标记的六肽（简称为Cyp-GRD）。在体外，Cyp-GRD被非小细胞肺癌细胞（A549）内化，在浓度高达1×10⁻⁴ M时对细胞没有可观察到的细胞毒性或增殖影响。对注射到荷A549肿瘤小鼠体内的Cyp-GRD进行时域荧光强度和寿命成像显示，该探针优先在肿瘤和主要排泄器官中积累。绘制了肿瘤部位共轭物的荧光寿命，显示了与其环境相关的寿命的空间分布。此外，通过对时间分辨强度进行积分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。对那些具有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，表明肿瘤具有更高的平均寿命，反映了肿瘤生理病理学的改变。本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。
