剂量、干预时间和放射性核素对碘化钠转运体（NIS）靶向放射性核素治疗的影响。

Effects of dose, intervention time, and radionuclide on sodium iodide symporter (NIS)-targeted radionuclide therapy.

作者信息

Shen D H Y, Marsee D K, Schaap J, Yang W, Cho J-Y, Hinkle G, Nagaraja H N, Kloos R T, Barth R F, Jhiang S M

机构信息

Department of Physiology and Cell Biology, College of Medicine and Public Health, The Ohio State University, Columbus, OH 43210-1218, USA.

出版信息

Gene Ther. 2004 Jan;11(2):161-9. doi: 10.1038/sj.gt.3302147.

DOI:10.1038/sj.gt.3302147

PMID:14712300

Abstract

The sodium iodide symporter (NIS) mediates iodide uptake into thyrocytes and is the molecular basis of thyroid radioiodine therapy. We previously have shown that NIS gene transfer into the F98 rat gliomas facilitated tumor imaging and increased survival by radioiodine. In this study, we show that: (1) the therapeutic effectiveness of (131)I in prolonging the survival time of rats bearing F98/hNIS gliomas is dose- and treatment-time-dependent; (2) the number of remaining NIS-expressing tumor cells decreased greatly in RG2/hNIS gliomas post (131)I treatment and was inversely related to survival time; (3) 8 mCi each of (125)I/(131)I is as effective as 16 mCi (131)I alone, despite a smaller tumor absorbed dose; (4) (188)ReO(4), a potent beta(-) emitter, is more efficient than (131)I to enhance the survival of rats bearing F98/hNIS gliomas. These studies demonstrate the importance of radiopharmaceutical selection, dose, and timing of treatment to optimize the therapeutic effectiveness of NIS-targeted radionuclide therapy following gene transfer into gliomas.

摘要

碘化钠同向转运体（NIS）介导碘化物摄取进入甲状腺细胞，是甲状腺放射性碘治疗的分子基础。我们之前已经表明，将NIS基因导入F98大鼠胶质瘤可促进肿瘤显像并通过放射性碘延长生存期。在本研究中，我们发现：（1）¹³¹I延长荷F98/hNIS胶质瘤大鼠生存期的治疗效果呈剂量和治疗时间依赖性；（2）¹³¹I治疗后，RG2/hNIS胶质瘤中剩余表达NIS的肿瘤细胞数量大幅减少，且与生存期呈负相关；（3）尽管肿瘤吸收剂量较小，但¹²⁵I/¹³¹I各8 mCi与单独使用16 mCi ¹³¹I效果相同；（4）强效β⁻发射体¹⁸⁸ReO₄比¹³¹I更能有效延长荷F98/hNIS胶质瘤大鼠的生存期。这些研究证明了放射性药物的选择、剂量和治疗时机对于优化胶质瘤基因转移后NIS靶向放射性核素治疗的疗效至关重要。