Shimura H, Haraguchi K, Miyazaki A, Endo T, Onaya T
The Third Department of Internal Medicine, Yamanashi Medical University, Japan.
Endocrinology. 1997 Oct;138(10):4493-6. doi: 10.1210/endo.138.10.5571.
131I therapy is a widely accepted treatment for differentiated thyroid cancers which can accumulate iodide. We evaluated the efficiency of 131I therapy against tumors which are transfected with the Na+/I- symporter (NIS) gene. We transfected the rat NIS cDNA expression vector into malignantly transformed rat thyroid cells (FRTL-Tc) which do not concentrate iodide. The resultant cell line (Tc-rNIS) accumulated 125I 60-fold in vitro. The FRTL-Tc cells formed solid tumors after injection of cells into subcutaneous tissues of Fischer 344 rats. Tumors formed with Tc-rNIS cells accumulated up to 27.3% of total 125I administered, and concentrated 125I 11 to 27-fold in the tumors. Extracorporeal measurement of radioactivity in the tumors revealed that 125I accumulation peaked at 90 min, and decreased to half levels 6 h after the injections. To investigate the effect of 131I administration on the tumor growth, we injected Na131I 2 and 3 weeks after the transplantation of the cells. The Na131I did not change the tumor volume significantly in either the FRTL-Tc or the Tc-rNIS-induced tumors. The short (6 h) effective half life of 131I in the tumors diminished the radiation dose to the tumor cells. However, this approach may prove beneficial in the treatment of radiosensitive cancers, and could be employed diagnostically.
131I治疗是一种广泛接受的针对可摄取碘的分化型甲状腺癌的治疗方法。我们评估了131I治疗对转染了钠/碘同向转运体(NIS)基因的肿瘤的疗效。我们将大鼠NIS cDNA表达载体转染到不摄取碘的恶性转化大鼠甲状腺细胞(FRTL-Tc)中。所得细胞系(Tc-rNIS)在体外摄取125I的能力提高了60倍。将FRTL-Tc细胞注射到Fischer 344大鼠的皮下组织后形成实体瘤。用Tc-rNIS细胞形成的肿瘤摄取了高达27.3%的注入的总125I,并且肿瘤中125I的富集倍数为11至27倍。对肿瘤放射性的体外测量显示,125I摄取在90分钟时达到峰值,并在注射后6小时降至一半水平。为了研究给予131I对肿瘤生长的影响,我们在细胞移植后2周和3周注射Na131I。Na131I对FRTL-Tc或Tc-rNIS诱导的肿瘤的肿瘤体积均无显著影响。131I在肿瘤中的短有效半衰期(6小时)降低了对肿瘤细胞的辐射剂量。然而,这种方法可能对放射敏感性癌症的治疗有益,并且可用于诊断。