^(99m)Tc标记的生长抑素受体介导的肝癌肺转移显像的实验研究

Somatostatin Receptor Mediated Scintigraphy on Primary Human Hepatocellular Carcinoma with Pulmonary Metastasis

[目的]为99mTc标记生长抑素类似物奥曲肽对原发性肝癌伴肺转移的诊断与靶向放疗提供实验依据。[方法]用RT-PCR检测高转移潜能的人肝细胞癌株HCCLM6的生长抑素受体2mRNA的表达并测序;建立裸鼠原位肝癌肺转移模型;人工合成99mTc-DOTA-D-Phe1-Tyr3-Octreotide并用于荷瘤裸鼠显像,观察原位肿瘤组织、肺转移瘤及重要器官组织的99mTc-DOTA-D-Phe1-Tyr3-Octreotide摄取分布状况,并比较各组织的摄取比值(T/B)。[结果]RT-PCR和测序结果证实人肝癌细胞株HCCLM6特异高表达生长抑素受体2,扫描结果可见原位肝癌组织、肺转移瘤组织有明显的99mTc-DOTA-D-Phe1-Tyr3-Octreotide摄取,脑、心及正常肺组织等未见明显99mTc-DOTA-D-Phe1-Tyr3-Octreotide聚集,肾脏和膀胱可见明显99mTc-DOTA-D-Phe1-Tyr3-Octreotide放射性浓聚影。[结论]人肝癌细胞株HCCLM6高表达生长抑素受体2,在该受体介导下99mTc-DOTA-D-Phe1-Tyr3-Octreotide能够与原位肝癌及肺转移性肝癌特异结合,可能为放射性核素标记奥曲肽用于原发性肝癌肺转移的诊断及靶向放疗提供一定的理论基础。

[Purpose] To provide experimental evidence of targeting radiotherapy using 99mTc labelled octreotide on primary human hepatocellular carcinoma（HCC）with pulmonary metastasis.[Methods] The expression of SSTR2 mRNA in human hepatocellular carcinoma cell line HCCLM6 was measured by reverse transcriptase polymerase chain reaction（RT-PCR）.The assay was performed in tumor bearing BALB/c nude mouse.The uptake ratio（T/B） of 99mTc in malignant tissues and normal organs were calculated.[Results] RT-PCR showed SSTR2 mRNA was highly expressed in HCCLM6 cell line.Scintigraphy demonstrated that 99mTc was absorbed by the orthotopic xenograft HCC as well as the pulmonary metastatic foci.99mTc also congregated at bladder and kidney due to the urine secretion.99mTc was almost absent at heart,brain and normal pulmonary tissues.[Conclusion] Primary HCC with pulmonary metastasis can be scanned by SSTR2 mediated 99mTc-DOTA-D-Phe1-Tyr3-Octreotide scintigraphy.This study probably provide theoretical evidence of localizable diagnosis as well as targeting radiotherapy using isotope labeled somatostatin analogues on HCC with pulmonary metastasis.