Dadachova Ekaterina, Nguyen Andrew, Lin Elaine Y, Gnatovskiy Leo, Lu Ping, Pollard Jeffrey W
Department of Nuclear Medicine, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Nucl Med Biol. 2005 Oct;32(7):695-700. doi: 10.1016/j.nucmedbio.2005.05.007.
Novel therapeutic modalities are needed for breast cancer patients in whom standard treatments are not effective. Mammary gland sodium/iodide symporter has been identified as a molecular target in breast cancers in humans and in some transgenic mouse models. We report the results of a therapy study with (131)I(-) and (188)ReO(4)(-) of breast cancer in polyoma middle T oncoprotein (PyMT) transgenic mice endogenously expressing the Na(+)/I(-) symporter (NIS).
PyMT mice (12-13 weeks old) with one palpable tumor of 0.5-0.8 cm in diameter were used. For the therapy studies, PyMT mice were (1) treated with two intraperitoneal injections of 1.5 mCi of (188)ReO(4)(-) 1 week apart, (2) pretreated for 1 week with 5 microg of triiodothyronine (T3) followed by two intraperitoneal injections of 1.5 mCi of (131)I(-) 1 week apart or (3) left untreated. The tumor and normal organ uptakes were assessed by scintigraphic imaging. The thyroid function of treated and control animals was evaluated at the completion of the study by measuring the T3/thyroxine (T4) ratio in their blood.
There was significant uptake of (131)I(-) and (188)ReO(4)(-) in the primary palpable tumors as well as in nonpalpable tumors, stomachs and thyroids. The tumor uptake after the second injection was 10 times lower in comparison with the first injection. Tumor growth was significantly inhibited in both the (131)I(-) and (188)ReO(4)(-) groups in comparison with the control group, and tumors in the (188)ReO(4)(-) group increased in size significantly less than in the (131)I(-) group. The T3/T4 ratios were calculated to be 27 and 25 for the control group and the (188)ReO(4)(-) group, respectively; for (131)I(-), both the T3 and T4 levels were below detection limit, demonstrating much less effect on the thyroids of treatment with (188)ReO(4)(-) than with (131)I(-).
These results prove that NIS expression in breast tumors in animal models allows specific, efficient and safe treatment with a variety of radionuclides transported by NIS.
对于标准治疗无效的乳腺癌患者，需要新的治疗方式。乳腺钠/碘同向转运体已被确定为人类乳腺癌和一些转基因小鼠模型中的分子靶点。我们报告了一项针对内源性表达钠/碘同向转运体（NIS）的多瘤病毒中间T抗原（PyMT）转基因小鼠乳腺癌进行的（131）I⁻和（188）ReO₄⁻治疗研究结果。
使用12 - 13周龄、有一个直径0.5 - 0.8 cm可触及肿瘤的PyMT小鼠。在治疗研究中，PyMT小鼠被分为：（1）间隔1周腹腔注射两次1.5 mCi的（188）ReO₄⁻；（2）用5 μg三碘甲状腺原氨酸（T3）预处理1周，然后间隔1周腹腔注射两次1.5 mCi的（131）I⁻；（3）不进行治疗。通过闪烁成像评估肿瘤和正常器官的摄取情况。在研究结束时，通过测量血液中的T3/甲状腺素（T4）比值来评估治疗组和对照组动物的甲状腺功能。
在可触及的原发性肿瘤以及不可触及的肿瘤、胃和甲状腺中，（131）I⁻和（188）ReO₄⁻均有显著摄取。第二次注射后的肿瘤摄取量比第一次注射低10倍。与对照组相比，（131）I⁻组和（188）ReO₄⁻组的肿瘤生长均受到显著抑制，且（188）ReO₄⁻组肿瘤大小的增加明显小于（131）I⁻组。对照组和（188）ReO₄⁻组的T3/T4比值分别计算为27和25；对于（131）I⁻，T3和T4水平均低于检测限，表明（188）ReO₄⁻治疗对甲状腺的影响远小于（131）I⁻。
这些结果证明，动物模型中乳腺肿瘤的NIS表达允许使用NIS转运的多种放射性核素进行特异性、高效且安全的治疗。
