非小细胞肺癌荷瘤鼠^(99m)Tc-acetate-octreotide显像与生长抑素受体表达水平的实验研究

Expression of somatostatin receptor and the correlation with ^(99m)Tc-acetate-octreotide imaging in vivo for detect the non-small cell lung cancer

目的:探讨非小细胞肺癌(NSCLC)荷瘤鼠模型肿瘤组织中生长抑素受体(SSTR)的表达水平与99mTc-acetate-octreotide显像的相关性研究。方法:体外培养NSCLC细胞株SPC-A1,种植于balb/c裸鼠皮下成瘤,建立人NSCLC荷瘤鼠模型;行99mTc-acetate-octreotide显像,勾画ROI计算肿瘤与对侧正常组织(N/NT)放射性比值,并测定肿瘤及主要脏器单位组织的放射性摄取百分值(%ID/g),采用逆转录-聚合酶反应(RT-PCR)检测肿瘤组织中各SSTR亚型mRNA的表达水平,对SSTR亚型表达水平与T/NT放射性摄取比值进行相关性研究。结果:99mTc-acetate-octreotide NSCLC荷瘤鼠模型显像示肿瘤部位有较高的放射性浓聚,与对侧正常组织T/NT比值较高,4h达2.38±0.09;99mTc-acetate-octreotide荷瘤鼠体内生物学分布示药物在肿瘤部位有较高的摄取;RT-PCR示NSCLC组织中有着丰富的SSTR表达,SSTR3、SSTR5亚型表达水平较高,其中SSTR5的mRNA表达水平与肿瘤显像阳性荷瘤鼠T/NT比值呈正相关(r=0.93,P<0.01)。结论:NSCLC细胞株SPC-A1高表达SSTR3和SSTR5,其中SSTR5表达水平与肿瘤组织对99mTc-acetate-octreotide的摄取呈正相关。99mTc-acetate-octreotide受体显像对NSCLC有较好的影像诊断价值。

Objective：To evaluate the correlation between the expression of somatostatin receptor （SSTR） in tumor tissue and the 99mTc-acetate-octreotide scintigraphy of non-small cell lung cancer（NSCLC）. Methods：Nude mice bearing human NSCLC model were established. 99mTc-acetate-octreotide imaging was performed in NSCLC model, and＇the ratio of tumor to normal tissue（T/NT） was calculated over ROI to observe the radioactive uptake. The biodistribution was studied. The mRNA expression of SSTR in tumor tissue was detected by RT-PCR to evaluate the correlation between the expression of SSTR in tumor tissue and the 99mTc-acetate-octreotide scintigraphy of NSCLC. Results：Static planar image showed that the tumor had focal uptake of 99mTc-acetate-octreotide. Four hours after 99mTc-acetate-octreotide administration,the T/NT ratio was 2.38 ± 0.09. The biodistribution showed high uptake of the tracer in tumor;high expression of SSTR3 and SSTR5 in NSCLC,especially SSTR5. Positive correlation were obtained between the T/NT ratio and the expression of SSTR5 mRNA （r = 0.93,P 〈 0.01）. Conclusion：SSTR3 and SSTR5 are highly expressed in NSCLC cell line, especially SSTR5. There is a significant correlation between the tumor uptake of 99mTc-acetate-octreotide and SSTR5 mRNA expression. This approach may provide a basis for SSTR targeted diagnosis and therapy of human NSCLC.