Department of Radiation Oncology, Box 356069, University of Washington, Seattle, WA 98195 USA.
Nucl Med Biol. 2012 Nov;39(8):1161-6. doi: 10.1016/j.nucmedbio.2012.07.007. Epub 2012 Sep 15.
3'-Fluoro-3'-deoxythymidine (FLT) has been proposed for positron emission tomography (PET)-based identification of tumor chemosensitivity that is mediated by the human equilibrative nucleoside transporter-1 (ENT1). ENT1 facilitates transport of FLT into cells and elevated levels of FLT are associated with both larger FLT-PET signals and increased response to nucleoside-based chemotherapies. FLT-PET is also used as a measure of tumor proliferation. The present study examined the extent to which ENT1 levels vary in a proliferation-dependent manner in tumor cells in vivo.
The human adenocarcinoma cell line A549 was used to establish tumor xenografts in nude mice. FLT uptake was measured in vivo using PET, and further examined ex vivo using autoradiography. FLT uptake patterns were compared to immunohistochemical (IHC) analysis of ENT1 and the proliferation markers Ki67 and BrdU.
Regional differences in FLT uptake matched differences in IHC proliferation markers. All cells stained for ENT1, but the staining intensity was twice as high for Ki67(+) cells than for Ki67(-) cells.
Under in vivo conditions, proliferating regions of tumors show increased FLT uptake and higher ENT1 levels than nonproliferating tumor regions.
3'-氟-3'-脱氧胸苷（FLT）已被提议用于正电子发射断层扫描（PET）基于肿瘤化疗敏感性的鉴定，这种鉴定是由人平衡核苷转运蛋白-1（ENT1）介导的。ENT1 促进 FLT 进入细胞，并且高水平的 FLT 与更大的 FLT-PET 信号和增加对基于核苷的化疗的反应都有关。FLT-PET 也被用作肿瘤增殖的测量。本研究检查了在体内肿瘤细胞中以增殖依赖性方式变化的 ENT1 水平的程度。
使用人腺癌细胞系 A549 在裸鼠中建立肿瘤异种移植物。使用 PET 在体内测量 FLT 摄取，并使用放射自显影进一步在体外检查。FLT 摄取模式与 ENT1 和增殖标志物 Ki67 和 BrdU 的免疫组织化学（IHC）分析进行比较。
FLT 摄取的区域差异与 IHC 增殖标志物的差异相匹配。所有细胞均对 ENT1 染色，但 Ki67(+)细胞的染色强度是 Ki67(-)细胞的两倍。
在体内条件下，肿瘤的增殖区域显示出比非增殖肿瘤区域更高的 FLT 摄取和更高的 ENT1 水平。
