摘要
目的探讨^99Tc^m-2-（2．甲基-5-硝基-1H-咪唑-1-基）磷酸乙酯（MNLS，甲硝唑磷酸酯）乏氧显像监测荷瘤小鼠肿瘤放疗后乏氧状态变化的可行性。方法（1）建立荷H22肝癌细胞小鼠模型，待肿瘤直径约1cm时，注射7．4MBq^99Tc^m-MNLS后进行显像，观察注射显像剂后30min，1、2、3、4、6和8h（各时间组小鼠均为6只）乏氧显像情况并确定最佳显像时间。显像后处死荷瘤小鼠，计算各时间点各组织％ID／g。（2）放疗组及其对照组荷H22肝癌细胞小鼠行即刻、24h、48h^99Tc^m-MNLS显像（各组小鼠均为6只，放疗组小鼠肿瘤部位给予25Gy放射治疗，对照组不予放疗），应用ROI技术测定T／NT（对侧部位），肿瘤标本行HIF-1d免疫组织化学染色，探讨放疗组及对照组T／NT与HIF-1d表达量的相关性。（3）应用SPSS17．0软件对数据进行单因素方差分析、最小显著差异t检验、两样本t检验及Spearman相关分析。结果（1）^99Tc^m-MNLS在肿瘤组织摄取早，2h显像最佳，^99Tc^m-MNLS主要通过。肾脏排泄。（2）放疗后24h显像组T／NT（2．65±0．27）、HIF—1α表达量[（50．62±3．78）％]低于aped显像组[3．35±0．19、（85．32±0．94）％，t=5．640、6．701，均P〈0．05]，高于48h显像组[2．23±0．52、（21．69±0．75）％，t=7．674、4．911，均P〈0．05]；放疗后即刻显像组T／NT比值、HIF-1α表达量均较相应对照组[2．74±0．29、（28．26±1．70）％]增高（t=4．235、3．473，均P〈0．05）；放疗后24h显像组T／NT比值、HIF-1α表达量较相应对照组[2．98±0．16、（58．45±0．98）％]差异均无统计学意义（t=0．525、2．043，均P〉0．05）；放疗后48h显像组rr／NT比值、HIF-1α表达量均较相应对照组[3．15±0．88、（67．64±3．55）％]降低（t=7．902、3．258，均P〈0．05）。放疗组不同时间点各显像组TT／NT与HIF-1仪表达量呈正相关（n=0．793，P〈0．05），对照组不同时间点各显像组T／NT与HIF-1α表达量呈正相关（rs=0．756，P〈0．05）。结论^99Tc^mMNLS肿瘤乏氧显像可以评估荷瘤小鼠肿瘤放疗后乏氧状态变化。
Objective To investigate the feasibility of monitoring the tumor＇s hypoxic changes by ^99Te^m- 2-（2-methyl-5-nitro-lH-imidazol-l-yl） ethyl eihydrogen phosphate （MNLS） imaging after radiotherapy. Methods （ 1 ） H22 cells were cultured and mice model with liver cancer xenografte was made. The mice were imaged at 0.5, 1, 2, 3, 4, 6 and 8 h （ six mice in each group） after injected with 7.4 MBq ^99Tc^m- MNLS when the tumor size reach about 1 cm. Then the mice were sacrificed. The T/NT and %ID/g of each time point was calculated. （2） The liver cancer bearing mice of radiotherapy group （25 Gy ） and control group were imaged at 0, 24, 48 h, and then the technique of ROI was adopted to calculate the T/NT at each time point in the two groups. Immunohistochemical stain method was used to evaluate the expression level of HIF-1α in liver cancer. （3） One-way analysis of variance, the least significant difference t test, two-sample t test and Spearman correlation analysis were performed. Results （ 1 ） The uptake of 99Tcm- MNLS in the liver cancer bearing mice was significant at 2 h after injection and the %ID/g was the highest. ^99Tc^m-MNLS was excreted mainly through kidneys. （2） The T/NT and HIF-1α expression level in radiotherapy group at 24 h （2.65±0.27, （50.62±3.78）%） were lower than those at the instant （3.35±0.19, （85.32± 0.94）%, t=5.640, 6.701, both P〈0.05）, but higher than those at 48 h （2.23±0.52, （21.69±0.75）%, t=7.674, 4.911, both P〈0.05）. The T/NT and HIF-1α expression in the radiotherapy group were significantly higher than those in the control group at the instant （ 2.74 ± 0.29, （ 28.26 ± 1.70） %, t = 4.235, 3. 473, both P〈0.05） but lower at 48 h （3.15±0.88, （67.64±3.55）%,t=7.902, 3.258, both P〈0.05）. However, no significant differenee was observed at 24 h between radiotherapy group and the control group （2.98±0.16, （58.45±0.98）%, t=0.525, 2.043, both P〉0.05）. The ehange of T/NT elosely eorrelated with the expression of HIF-loL in both the radiotherapy group and eontrol group（ r, = 0.793, 0.756, both P〈 0.05）. Conclusion ^99Tc^m-MNLS hypoxia imaging has potential to monitor changes of hypoxia in tumor after radiotherapy.
出处
《中华核医学与分子影像杂志》
CSCD
北大核心
2013年第5期367-371,共5页
Chinese Journal of Nuclear Medicine and Molecular Imaging
