【摘要】 目的探讨活体肿瘤细胞凋亡监测作为评价肿瘤对化疗反应的一种新方法的可行性。方法细胞凋亡分子探针99Tcm-HYNIC-AnnexinⅤ经化学和放射化学合成获得。20~25 g昆明种小白鼠右前腋下皮下组织接种S-180肉瘤,建立荷肿瘤小鼠模型。荷瘤小鼠在环磷酰胺腹腔内给药化疗8 h2、4 h4、8 h7、2 h后,分别尾静脉注射99Tcm-HYNIC-AnnexinⅤ,1 h后进行单光子发射型计算机断层显像(SPECT)和体内生物分布测定,并与对照组进行比较。根据化疗后显像的最佳时间,给荷瘤小鼠尾静脉注射99Tcm-DTPA-HSA,测定体内各组织器官的血流分布情况。所有体内生物分布的实验结果应用SPSS 10.0统计学软件进行统计学分析。结果荷瘤小鼠在环磷酰胺腹腔内给药化疗后72 h进行SPECT显像时,肿瘤的显像效果最明显,且体内生物分布测定显示在化疗后72 h的肿瘤组织的放射性摄取值(1.87±0.58)最高,是对照组(1.18±0.128)的1.58倍(二者比较,P<0.05),与显像结果具有一致性。肿瘤/肌肉(T/M)放射性摄取率之比为5.83±0.799,肿瘤/血液(T/B)为1.03±0.258,与对照组比较均为P<0.05。化疗组和对照组的肿瘤组织对99Tcm-DTPA-HSA的摄取无明显差异(P>0.05)。结论在进行单次环磷酰胺腹腔内给药化疗后72 h,荷瘤小鼠的肿瘤组织对99Tcm-HYN-IC-AnnexinⅤ的摄取显著增加,细胞凋亡体内显像作为一种评价肿瘤对化疗反应的无创性的监测方法是有效、可行的。更多还原

【Abstract】 Objective To investigate the effectiveness and feasibility of in vivo cell apoptosis imaging of tumor response after a single dose of chemotherapy.Methods（）⁹⁹Tc^m-HYNIC-Annexin Ⅴ as cell apoptosis molecular probe was obtained through chemical and radiochemical synthesis.Seven days after being inoculated with S-180 sarcoma in the right upper limbs,the mice weighed 20-25 g were randomized to receive a single dose of cyclophosphamide（150 mg/kg intraperitoneally） as trial groups or to receive the same volume of physiological saline as controls.Having been received cyclophosphamide 8 h,24 h,48 h and 72 h later,the mice were injected（）⁹⁹Tc^m-HYNIC-Annexin Ⅴ by tail vein.Imaging and radioactivity in tissues were obtained at 1 h postinjection of molecular probe.（）⁹⁹Tc^m-DTPA-HSA was used as a marker of tumor blood flow.All results of radioactivity in tissues were analyzed by the statistic software of SPSS 10.0.Results Cyclophosphamide treatment significantly increased the uptake（percentage activity of injected dose per gram of tissue ） of(（）⁹⁹Tc^m-)HYNICAnnexin Ⅴ in tumor.The optimum imaging time after a single dose of chemotherapy could be considered at 72 h postinjection（[1.87±0.58]%ID/g for treated 72 h mice tumor-bearing and [1.18±0.128]%ID/g for controls,P<0.05）.The ratio（[5.83±0.799]%ID/g） of tumor/muscle was higher than those of tumor/blood（[1.03±0.258]%ID/g） and controls with significant difference（P<0.05）.（）⁹⁹Tc^m-DTPA-HSA uptake was not significantly different in the treated and untreated groups,which indicated the increased accumulation of（）⁹⁹Tc^m-HYNIC-Annexin Ⅴ in the tumor is not attributable to changes in blood flow.Conclusion The present study shows that the radioactive uptake of cell apoptosis in mice tumor-bearing is significantly increased at 72 h after a single dose of cyclophosphamide treatment.The current results suggest the potential（utility） of cell apoptosis imaging in vivo as a noninvasive means to assess tumor response after a single dose of chemotherapy.更多还原