Abd-Elgaliel Wael R, Cruz-Monserrate Zobeida, Logsdon Craig D, Tung Ching-Hsuan
Department of Radiology, The Methodist Hospital Research Institute, Weill Cornell Medical College, 6565 Fannin Street, B5-009, Houston, TX 77030, USA.
Department of Cancer Biology, University of Texas, M. D. Anderson Cancer Center, Houston, TX, USA.
Mol Biosyst. 2011 Dec;7(12):3207-3213. doi: 10.1039/c1mb05215b. Epub 2011 Sep 20.
The purpose of this study is to demonstrate the ability of imaging Cathepsin E (Cath E) positive tumors in living animals through selective targeting of Cath E proteolytic activity using a sensitive molecular imaging agent.
A peptide-based Cath E imaging probe and a control probe were synthesized for this study. Human Cath E-positive cancer cells (MPanc96-E) were implanted subcutaneously in nude mice. Tumor-bearing mice were examined in vivo with near-infrared fluorescence (NIRF) imaging at various time points after intravenous injection of the Cath E sensing imaging probe. Excised organs and tissues of interest were further imaged ex vivo.
Upon specific Cath E proteolytic activation, the NIRF signal of the imaging probe a was converted from an optically quenched initial state to a highly fluorescent active state. Imaging probe a was able to highlight the Cath E-positive tumors as early as 24 h post injection. Fluorescent signal in tumor was 3-fold higher than background. The confined specificity of imaging probe a to tumor associated Cath E was verified by using control imaging probe b. Both in vivo and ex vivo imaging results confirmed the superior selectivity and sensitivity of imaging probe a in Cath E imaging.
The small animal studies demonstrated the capability of probe a for imaging Cath E-positive tumors. The developed optical probe could be applied in early diagnostic imaging and guiding subsequent surgical procedure.
本研究的目的是通过使用一种灵敏的分子成像剂选择性靶向组织蛋白酶E（Cath E）的蛋白水解活性，来证明在活体动物中对Cath E阳性肿瘤进行成像的能力。
为本研究合成了一种基于肽的Cath E成像探针和一种对照探针。将人Cath E阳性癌细胞（MPanc96-E）皮下植入裸鼠体内。在静脉注射Cath E传感成像探针后的不同时间点，对荷瘤小鼠进行近红外荧光（NIRF）成像体内检查。对切除的感兴趣器官和组织进行进一步的体外成像。
在特定的Cath E蛋白水解激活后，成像探针a的NIRF信号从光学淬灭的初始状态转变为高荧光活性状态。成像探针a在注射后24小时就能突出显示Cath E阳性肿瘤。肿瘤中的荧光信号比背景高3倍。通过使用对照成像探针b验证了成像探针a对肿瘤相关Cath E的局限性特异性。体内和体外成像结果均证实了成像探针a在Cath E成像中的卓越选择性和敏感性。
小动物研究证明了探针a对Cath E阳性肿瘤进行成像的能力。所开发的光学探针可应用于早期诊断成像并指导后续手术操作。
