Tavri Sidhartha, Jha Priyanka, Meier Reinhard, Henning Tobias D, Müller Tina, Hostetter Daniel, Knopp Christiane, Johansson Magnus, Reinhart Verena, Boddington Sophie, Sista Akhilesh, Wels Winfried S, Daldrup-Link Heike E
Department of Radiology, University of California-San Francisco, San Francisco, CA 941143-0628, USA.
Mol Imaging. 2009 Jan-Feb;8(1):15-26.
The purpose of this study was to track fluorophore-labeled, tumor-targeted natural killer (NK) cells to human prostate cancer xenografts with optical imaging (OI). NK-92-scFv(MOC31)-zeta cells targeted to the epithelial cell adhesion molecule (EpCAM) antigen on prostate cancer cells and nontargeted NK-92 parental cells were labeled with the near-infrared dye DiD (1,1'-dioctadecyl-3,3,3',3'-tetramethylindodicarbocyanine). The fluorescence, viability, and cytotoxicity of the labeled cells were evaluated. Subsequently, 12 athymic rats with prostate cancer xenografts underwent OI scans before and up to 24 hours postinjection of DiD-labeled parental NK-92 cells or NK-92-scFv(MOC31)-zeta cells. The tumor fluorescence intensity was measured and compared between pre- and postinjection scans and between both groups using t-tests. OI data were confirmed with fluorescence microscopy. In vitro studies demonstrated a significant increase in the fluorescence of labeled cells compared with unlabeled controls, which persisted over a period of 24 hours without any significant change in the viability. In vivo studies demonstrated a significant increase in tumor fluorescence at 24 hours postinjection of tumor-targeted NK-92-scFv(MOC31)-zeta cells but not parental NK cells. Ex vivo OI scans and fluorescence microscopy confirmed a specific accumulation of NK-92-scFv(MOC31)-zeta cells but not parental NK cells in the tumors. Tumor-targeted NK-92-scFv(MOC31)-zeta cells could be tracked to prostate cancer xenografts with OI.
本研究的目的是利用光学成像（OI）追踪荧光团标记的、靶向肿瘤的自然杀伤（NK）细胞至人前列腺癌异种移植瘤。靶向前列腺癌细胞上皮细胞黏附分子（EpCAM）抗原的NK-92-scFv（MOC31）-ζ细胞和非靶向的NK-92亲本细胞用近红外染料DiD（1,1'-二辛基-3,3,3',3'-四甲基吲哚二碳菁）标记。对标记细胞的荧光、活力和细胞毒性进行了评估。随后，12只患有前列腺癌异种移植瘤的无胸腺大鼠在注射DiD标记的亲本NK-92细胞或NK-92-scFv（MOC31）-ζ细胞之前及注射后长达24小时接受OI扫描。测量肿瘤荧光强度，并使用t检验比较注射前和注射后扫描之间以及两组之间的荧光强度。OI数据通过荧光显微镜得到证实。体外研究表明，与未标记的对照相比，标记细胞的荧光显著增加，并且在24小时内持续存在，活力没有任何显著变化。体内研究表明，注射靶向肿瘤的NK-92-scFv（MOC31）-ζ细胞后24小时肿瘤荧光显著增加，但亲本NK细胞注射后未出现这种情况。离体OI扫描和荧光显微镜证实，NK-92-scFv（MOC31）-ζ细胞而非亲本NK细胞在肿瘤中特异性聚集。靶向肿瘤的NK-92-scFv（MOC31）-ζ细胞可以通过OI追踪至前列腺癌异种移植瘤。
