胰腺癌生长抑素受体报告基因表达与其靶向显像的相关性研究

Expression of somatostatin receptor reporter gene and its correlation with targeted imaging in vivo for detection of pancreas carcinoma

目的探讨荷胰腺癌裸鼠模型肿瘤组织生长抑素受体(SSTR)报告基因的mRNA表达水平与99mTc-sandostatin显像对肿瘤的靶向诊断价值及二者的相关性。方法建立荷胰腺癌动物模型,对18只荷胰腺癌裸鼠模型行99mTc-sandostatin显像,勾画感兴趣区,计算瘤体与对侧正常组织的放射性比值(T/NT),用RT-PCR方法检测肿瘤组织SSTR1、SSTR2、SSTR5 mRNA的表达水平,对各SSTR亚型表达水平与T/NT比值进行相关性分析。结果13只荷胰腺癌裸鼠肿瘤清晰显影,瘤组织有较高的局灶性放射性浓聚;6 h T/NT比值达2.53±0.84。5只荷胰腺癌裸鼠显像弱阳性或阴性,6 hT/NT比值为1.04±0.06。肿瘤组织有SSTR1、SSTR2、SSTR5 mRNA表达,SSTR1、SSTR2的表达水平与肿瘤显像阳性裸鼠T/NT比值呈正相关,r分别为0.597(P<0.05)和0.807(P<0.01)。结论荷胰腺癌裸鼠肿瘤组织有SSTR表达,SSTR2尤为显著9。9mTc-sandostatin受体显像对荷胰腺癌动物模型有很好的靶向诊断价值;肿瘤99mTc-sandostatin摄取程度同SSTR1、SSTR2表达水平正相关。

Objective To evaluate the value of ^99mTc-sandostatin scintigraphy in targeted diagnosis of pancreas carcinoma and the correlation with expression of somatostatin receptor （SSTR） reporter gene in tumor tissue. Methods Nude mice bearing human pancreas carcinoma xenograft were established in advance. ^99mTc-sandostatin imaging was performed in 18 nude mice and tumor to normal tissue ratio （T/NT） was calculated, mRNA expression of SSTR1, SSTR2 and SSTR5 in tumor tissue was detected by RT-PCR. Results Out of 18 nude mice, 13 mice showed intense uptake of ^99mTc-sandostatin. Six hours after ^99mTc-sandostatin administration, the T/NT ratio was 2.53 ±0.84. Five mice showed negative findings, and the T/NT ratio was 1.04 ± 0.06. Positive correlations were obtained between the T/NT ratio and the expression of SSTR1 and SSTR2 mRNA , especially SSTR2 （r=0.807, P〈0.01）. Conclusion High expression of SSTR1, SSTR2 and SSTR5 mRNA were found in human pancreas tumor xenograft in nude mice, especially SSTR2. There is a significant correlation between the tumor uptake of ^99mTc-sandostatin and SSTR2 mRNA level. This approach may allow SSTR-targeted diagnosis and therapy of human pancreas cancer.