Sodium Iodide Symporter (NIS)-Mediated Radionuclide (131I, 188Re) Therapy of Liver Cancer After Transcriptionally Targeted Intratumoral in Vivo NIS Gene Delivery
Sodium Iodide Symporter (NIS)-Mediated Radionuclide (131I, 188Re) Therapy of Liver Cancer After Transcriptionally Targeted Intratumoral in Vivo NIS Gene Delivery
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DOI：
10.1089/hum.2010.158
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发表时间：
2011-11-01
影响因子：
4.2
通讯作者：
Spitzweg, Christine
中科院分区：
文献类型：
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作者：
Klutz, Kathrin;Willhauck, Michael J.;Spitzweg, Christine
我们报道了I-131对在肿瘤特异性甲胎蛋白（AFP）启动子控制下稳定表达钠碘同向转运体（NIS）的肝细胞癌（HCC）细胞的治疗效果。在本研究中，我们研究了腺病毒介导的体内NIS基因转移，然后给予I-131和Re-188治疗HCC异种移植物的疗效。我们使用复制缺陷型腺病毒携带的人NIS基因连接到小鼠AFP启动子（Ad 5-AFP-NIS）在体外和体内NIS基因转移。功能性NIS表达通过体内γ照相机成像确认，随后通过分析NIS蛋白和mRNA表达。用Ad 5-AFP-NIS感染的人HCC（HepG 2）细胞浓缩了50%的I-125的应用活性，这对于体外克隆形成测定中的治疗效果是足够高的。瘤内注射Ad 5-AFP-NIS（3 × 10（9）空斑形成单位）后4天，HepG 2异种移植物累积了14.5%注射剂量（ID）/g I-123，有效半衰期为13小时（肿瘤吸收剂量，318 mGy/MBq I-131）。相比之下，9.2%ID/g Re-188在肿瘤中累积，有效半衰期为12.8小时（肿瘤吸收剂量，545 mGy/MBq）。在HepG 2异种移植物中腺病毒介导的NIS基因转移后，给予治疗剂量的I-131或Re-188（55.5 MBq）导致肿瘤生长的显著延迟和存活率的改善，而Re-188和I-131之间没有显著差异。总之，在肿瘤特异性腺病毒介导的体内NIS基因转移后，I-131和Re-188在HepG 2异种移植物中表现出治疗效果。
We reported the therapeutic efficacy of I-131 in hepatocellular carcinoma (HCC) cells stably expressing the sodium iodide symporter (NIS) under the control of the tumor-specific alpha-fetoprotein (AFP) promoter. In the current study we investigated the efficacy of adenovirus-mediated in vivo NIS gene transfer followed by I-131 and Re-188 administration for the treatment of HCC xenografts. We used a replication-deficient adenovirus carrying the human NIS gene linked to the mouse AFP promoter (Ad5-AFP-NIS) for in vitro and in vivo NIS gene transfer. Functional NIS expression was confirmed by in vivo gamma-camera imaging, followed by analysis of NIS protein and mRNA expression. Human HCC (HepG2) cells infected with Ad5-AFP-NIS concentrated 50% of the applied activity of I-125, which was sufficiently high for a therapeutic effect in an in vitro clonogenic assay. Four days after intratumoral injection of Ad5-AFP-NIS (3 x 10(9) plaque-forming units) HepG2 xenografts accumulated 14.5% injected dose (ID)/g I-123 with an effective half-life of 13 hr (tumor-absorbed dose, 318 mGy/MBq I-131). In comparison, 9.2% ID/g Re-188 was accumulated in tumors with an effective half-life of 12.8 hr (tumor-absorbed dose, 545 mGy/MBq). After adenovirus-mediated NIS gene transfer in HepG2 xenografts administration of a therapeutic dose of I-131 or Re-188 (55.5 MBq) resulted in a significant delay in tumor growth and improved survival without a significant difference between Re-188 and I-131. In conclusion, a therapeutic effect of I-131 and Re-188 was demonstrated in HepG2 xenografts after tumor-specific adenovirus-mediated in vivo NIS gene transfer.