动物肿瘤模型乏氧水平的核素显像和乏氧诱导因子-1α的表达测定

Detecting Tumor Hypoxia Level of Animals' Tumors with SPECT Imaging and HIF-1α Expression

目的探讨肿瘤乏氧诱导因子1α(HIF1α)表达及乏氧显像剂99TcmEC甲硝唑(metronidazole,MNZ)SPECT显像对检测肿瘤乏氧(缺氧)程度的可行性,以及两种检测方法的相关性。方法建荷S180肉瘤的昆明小鼠和荷Lewis肺癌的C57/BL6两种肿瘤模型各12个,分别对两种荷瘤小鼠进行99TcmECMNZ的SPECT乏氧显像,显像结束后完整切取肿瘤组织,用免疫组化技术测定肿瘤HIF1α表达。结果S180肉瘤注射99TcmECMNZ后3hT/M(肿瘤放射性计数/对侧肌肉放射性计数)值为1.93～4.46(3.04±0.74),而HIF1α的表达为31.2%～60.8%(中位数为50.4%),两者间存在线性相关(t=2.732,P=0.021);Lewis肺癌T/M值为1.42～2.06(1.78±0.22),而HIF1α的表达则为0.1%～1.75%(中位数为1.1%),两者间无明显相关性(t=1.161,P=0.272)。S180肉瘤和Lewis肺癌的T/M值之间和HIF1α的表达之间均存在显著性差异(t′=5.69,P<0.01;t′=9.49,P<0.05)。结论99TcmECMNZ的SPECT乏氧显像和HIF1α的检测可用于判断不同类型的肿瘤和同一类型肿瘤之间的乏氧程度和差异。

Objective To evaluate the feasibility of HIF-1α(hypoxia induce factor-1α)expression and SPECT image with ^(99)Tc^m-EC-MNZ (^(99)Tc^m-EC-metronidazaole) in detecting tumor hypoxia,and to observe the correlation between these two methods. Method After models were set up, 12 Kunming mice bearing S180 sarcoma and 12 C57/BL6 mice bearing Lewis lung cancer were conducted by SPECT image with ^(99)Tc^m-EC-MNZ. Then tumor was resected and detected expression of HIF-1α by immunohistochemistry.Result The T/M ratio of S180 sarcoma 3h after injection of ^(99)Tc^m-EC-MNZ ranged from 1.93 to 4.46(3.04±0.74) and expression of HIF-1α of S180 sarcoma was 31.2%～60.8%(the median:50.4%). There was significant linear correlation between HIF-1α expression and T/M(t=2.732,P=0.021);The T/M ratio of Lewis lung cancer ranged from 1.42～2.06(1.78±0.22)and HIF-1α expression of Lewis lung cancer was 0.1%～1.75%(the median: 1.1%). No statistical correlation was observed between the T/M ratio and HIF-1α expression in Lewis cancer(t=1.161,P=0.272).Furthermore,there was significant difference between the T/M ratio of S180 sarcoma and that of lewis lung cancer;the HIF-α expression of S180 sarcoma and that of lewis lung cancer(t′=5.69,P<0.01;t′=9.49,P<0.05). Conclusion The present results suggest that SPECT image with 99Tcm EC MNZanddetection of HIF 1αcan predict hypoxic condition in different types of tumor and heterogeneity of hypoxia in the same type of cancer.