Treatment of transplanted tumor of lung adenocarcinoma A549 transfected by human somatostatin receptor subtype 2 (hsstr2) gene with 188Re-RC-160

Treatment of transplanted tumor of lung adenocarcinoma A549 transfected by human somatostatin receptor subtype 2 (hsstr2) gene with 188Re-RC-160
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188Re-RC-160治疗转染人生长抑素受体亚型2(hsstr2)基因的肺腺癌A549移植瘤。

DOI:
10.1016/j.nucmedbio.2010.05.007
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发表时间:
2010-11-01
影响因子:
3.1
通讯作者:
Wang, Jing
Wang, Jing
中科院分区:
医学4区
文献类型:
--
作者:
Zhao, Rong;Yang, Weidong;Wang, Jing

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背景和目标:放射性核素标记的生长抑素类似物选择性靶向生长抑素受体(SSTR)表达的肿瘤作为诊断和治疗这些肿瘤的基础。对生长抑素受体阴性的肿瘤,转染hSSTR 2基因。方法:采用Western blot法筛选稳定表达hSSTR 2的A549细胞(pcDNA 3-hSSTR 2 A549)和不表达生长抑素受体的A549细胞(pcDNA 3-A549)。随后建立了相应的动物肿瘤模型。使用188 Re-RC-160识别对hSSTR 2报告基因的表达进行成像。肿瘤生长抑素受体的表达进行了评价,使用免疫组织化学。通过肿瘤生长测定、苏木精-伊红染色、原位末端标记(TUNEL)法观察188 Re-RC-160对肿瘤的抑制作用。体内放射成像显示Re-188-RC-160对来自pcDNA 3-hSSTR 2 A549细胞的肿瘤的特异性靶向,与来自pcDNA 3 A549细胞的肿瘤相比。pcDNA 3-hSSTR 2 A549肿瘤生长抑制在单一7.4 MBq(ReRC)-Re-188-160处理组中显著高于2 × 7.4 MBq Re-188、RC-160组、对照组和pcDNA 3 A549肿瘤(P
Background and aim: Radionuclide-labeled somatostatin analogues selectively target somatostatin receptor (SSTR)-expressing tumors as a basis for diagnosis and treatment of these tumors. To those tumors without somatostatin receptor expressed, the hSSTR2 gene was transfected. Express of the hSSTR2 receptor was imaging and the radiotherapeutic effect was evaluated with Re-188-RC-160.Methods: The stable hSSTR2-expressing A549 cells (pcDNA3-hSSTR2 A549) and non-somatostatin receptor expressing A549 cells (pcDNA3 A549) were selected by western blot. Later, a corresponding animal tumor model was established. Expression of the hSSTR2 reporter was imaged using 188Re-RC-160 recognition. Tumors were evaluated for somatostatin receptor expression using immunohistochemistry. The distribution of 188Re-RC-160 in the animal tumor model was measured and the inhibitory effects of 188Re-RC-160 were evaluated by measurement of tumor growth and hematoxylin and eosin and TdT mediated dUTP nick end labeling (TUNEL) staining.Results: In vivo radioimaging revealed specific targeting of Re-188-RC-160 to tumors derived from pcDNA3- hSSTR2 A549 cells, compared to those from pcDNA3 A549 cells. pcDNA3- hSSTR2 A549 tumor growth inhibition was significantly higher in the single 7.4 MBq (ReRC)-Re-188-160 treatment group than in the 2x7.4 MBq rhenium-188, RC-160 group, control group, and pcDNA3 A549 tumors (P