A novel method of boron delivery using sodium iodide symporter for boron neutron capture therapy.

A novel method of boron delivery using sodium iodide symporter for boron neutron capture therapy.
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DOI:
10.1269/jrr.10036
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发表时间:
2010
影响因子:
2
通讯作者:
Brown SL
Brown SL
中科院分区:
医学4区
文献类型:
--
作者:
Kumar S;Freytag SO;Barton KN;Burmeister J;Joiner MC;Sedghi B;Movsas B;Binns PJ;Kim JH;Brown SL

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硼中子捕获疗法 (BNCT) 的有效性取决于癌细胞相对于正常组织细胞优先封存硼的情况。我们提出了一种使用表达碘化钠同向转运体(NIS)的腺病毒来隔离硼的新策略。通过直接肿瘤注射腺病毒,用 NIS 转染无胸腺小鼠皮下生长的人神经胶质瘤和原位大鼠脑肿瘤。转染几天后,全身施用以四氟硼酸钠(NaBF4)形式结合的硼。数小时后切除肿瘤并使用电感耦合等离子体原子发射光谱法评估硼浓度。在用 NIS 转染的人神经胶质瘤中,与未转染的肿瘤相比,使用 100 mg/kg NaBF4 时硼浓度高出 10 倍以上。在原位肿瘤模型中,与未转染的对侧正常脑相比,NIS 的存在使转染人病毒的大鼠肿瘤中的硼浓度几乎高出 4 倍。我们的结论是,表达 NIS 的腺病毒有潜力用作新型硼输送剂,并且应该在未来的临床应用中进行探索。
Boron Neutron Capture Therapy (BNCT) effectiveness depends on the preferential sequestration of boron in cancer cells relative to normal tissue cells. We present a novel strategy for sequestering boron using an adenovirus expressing the sodium iodide symporter (NIS). Human glioma grown subcutaneously in athymic mice and orthotopic rat brain tumors were transfected with NIS using a direct tumor injection of adenovirus. Boron bound as sodium tetrafluoroborate (NaBF4) was administered systemically several days after transfection. Tumors were excised hours later and assessed for boron concentration using inductively coupled plasma atomic emission spectroscopy. In the human glioma transfected with NIS, boron concentration was more than 10 fold higher with 100 mg/kg of NaBF4, compared to tumor not transfected. In the orthotopic tumor model, the presence of NIS conferred almost 4 times the boron concentration in rat tumors transfected with human virus compared with contralateral normal brain not transfected. We conclude that adenovirus expressing NIS has the potential to be used as a novel boron delivery agent and should be explored for future clinical applications.