hNIS基因转导黑色素瘤细胞介导放射性碘(^(125)I,^(131)I)摄取的体内实验

The in Vivo Study on Transfer of Human Sodium/Iodide Smporter Gene Enhancing Radioiodine (^(125)I,^(131)I)Uptake in Melanoma Cells

采用电转化法分别将含hNIS基因的重组质粒pc-DNA3-hNIS及空质粒pc-DNA3转导黑色素瘤细胞(B16),分别建立了细胞系B16-A和B16-B。将三种细胞系(B16-A、B16-B和B16)分别接种于C57小鼠右侧腹部皮下,当肿瘤生长至直径约10mm时进行131I全身显像;于注射125I后不同时相解剖肿瘤并测量其对125I的摄取量。结果显示:B16-A细胞系所成肿瘤见明显的放射性碘摄取,腹腔注射125I后1、2、4、12、24h每克肿瘤组织摄取125I放射性摄取百分数分别为12.22±0.71、10.91±0.72、8.73±0.99、1.24±0.29和0.19±0.03%ID/g。125I在B16-A肿瘤组织内的生物半衰期约为6h。对照组B16和B16-B细胞系所成肿瘤未见放射性碘摄取,两者相比,无统计学差异(P>0.05),将二组合并成一组作为对照,B16-A细胞系所成肿瘤摄碘量与之相比有显著差异,P<0.01。说明hNIS基因转导黑色素瘤细胞在体内足以介导放射性碘的摄取,但由于碘在肿瘤内的滞留时间较短,难以产生足够的治疗剂量。

To explore whether transfer of human sodium/iodide symporter (hNIS) gene in vivo can enhance radioiodine uptake in melanoma cells, pcDNA3hNIS and pcDNA3 are transduced into melanoma cells (B16) by electroporation, and two cell lines named B16A and B16B respectively are established. The three cell lines (B16A, B16B, and B16) are injected subcutaneously into the right flank of C57 mice. Biodistribution study and tumor imaging are performed when the tumor reaches approximately 10 mm in diameter. The imaging shows in vivo uptake in expected sites including the salivary glands, thyroid, stomach, and hNIStransduced tumor, whereas the nontransduced tumor is not visualized. The percentage of injected dose per gram(%ID/g) of B16A tumors at 1, 2, 4, 12, 24 h after injection of 125I are 12.22±0.71, 10.91±0.72, 8.73±0.99, 1.24±0.29, and 0.19±0.03 respectively, there are significantly difference between B16A and controlling tumors, P<0.01. However, biological T1/2 is about 6 hours. So, transfer of the hNIS gene can enhance radioiodine uptake in melanoma cells. However, the remaining time in the tumors is not long enough, and a lethal dose of radiation in tumor cells in vivo is too low to be available.