肿瘤组织~99Tc^m-EC-甲硝唑显像与乏氧诱导因子-1α表达水平的相关性研究

Experimental study of the correlation between ~99Tc^m-EC-MNZ SPECT imaging and the expression of hypoxia inducible factor-1αin tumor tissuse

目的探讨肿瘤组织^(99)Tc^m-双半胱氨酸(EC)-甲硝唑 SPECT 显像与乏氧诱导因子-1α(HIF-1α)表达水平的相关性。方法建立昆明小鼠 S180肉瘤肿瘤模型12个,对其进行^(99)Tc^m-EC-甲硝唑 SPECT 乏氧显像,测定其肿瘤/对侧肌肉放射性比值(T/M)。显像结束后即刻断颈处死小鼠,取出瘤体,用免疫组织化学法分别测定肿瘤组织 HIF-1α及其调控的下游基因血管内皮生长因子(VEGF)表达水平。结果 12只荷 S180肉瘤昆明小鼠注射^(99)Tc^m-EC-甲硝唑后3 h SPECT 显像的 T/M 为1.93～4.46(中位值3.13)。免疫组织化学结果显示表达 HIF-1α的细胞占31.2%～60.8%(中位值50.4%),与 T/M 呈直线相关(t=2.732,r=0.654,P=0.021);表达 VEGF 的细胞占33.8%～57.5%(中位值53.1%),与 HIF-1α表达细胞亦呈直线相关(t=3.011,r=0.690,P=0.0131)。结论肿瘤组织^(99)Tc^m-EC-甲硝唑 SPECT 显像与其 HIF-1α的表达水平呈线性相关,两者结合能较可靠地反映肿瘤组织的乏氧状况。

Objective To evaluate the correlation between ^99Tc^m-ethylene dicysteinc-metronidazaole （^99Tc^m-EC-MNZ） SPECT imaging and the expression of hypoxla inducible factor-let（HIF-let） in tumor tissue. Methods Twelve S180 sarcoma-bearing Kunming mice tumor models were established. Hypoxic imaging was obtained by SPECT with ^99Tc^m-EC-MNZ and the corresponding tumor/muscle ratios （T/M） were measured. Then the animals were sacrificed and the tumor specimen was resected, the expression of Hilt-let and vascular endothelial growth factor（VEGF） was measured by immunohistochemistry. Results Three hours after injection of ^99Tc^m-EC-MNZ, the T/M ranged from 1.93 to 4.46（ median 3.13）. The expression of HIF-1α ranged from 31.2% to 60.8% （ median 50.4% ） and was linearly correlated with the T/M （ t = 2. 732, r =0. 654, P =0. 021 ）. The expression of VEGF ranged from 33.8% to 57.5% （ median 53.1% ） and also linearly correlated with the expression of HIF-1α（ t = 3. 011 , r = 0. 690, P = 0. 0131 ）. Conclusions There is linear correlation between ^99Tc^m-EC-MNZ hypoxic SPECT imaging and the expression of HIF-1α. Combining them can reliably reflect the hypoxic status of the tumor.