凋亡显像剂^99mTc—HYNIC—annexin Ⅴ对肿瘤模型化疗疗效早期评价的可行性  

Feasibility of apoptosis-imaging agent ^99mTc-HYNIC-annexin Ⅴ in early assessment of chemotherapeutic effect on tumor models

作　　者：兰晓莉[1] 张永学[1] 何勇[1] 孙逊[1] 安锐[1] 高再荣[1] 曹国祥[1] 

机构地区：[1]华中科技大学同济医学院附属协和医院核医学科湖北省分子影像学重点实验室,武汉430022

出　　处：《中华肿瘤杂志》2008年第10期737-740,共4页Chinese Journal of Oncology

基　　金：高等学校博士学科点专项科研基金资助项目（20030487013）

摘　　要：目的评价凋亡显像剂^99mTc—HYNIC—annexin Ⅴ在肿瘤动物模型中对化疗疗效早期评估的可行性。方法人膜联蛋向Ⅴ（annexinⅤ）通过双功能螯合剂联肼尼克酰胺（HYNIC）进行^99mTc标记。在正常昆明小鼠右上肢接种Ehrlich腹水癌细胞，至肿瘤生长至1cm后，随机分为生理盐水处理组和环磷酰胺处理组（150mg／kg），并分别于处理后1h和24h时注射^99mTc—HYNIC—annexin Ⅴ，注射后30、60、180、360min进行双探头单光子发射计算机断层仪（SPECT）显像。图像分析采用感兴趣区（R01）技术，计算右上肢肿瘤部位与右下肢计数比值（肿瘤／下肢）。采用原位缺口末端标记（TUNEL）法检测肿瘤组织凋亡细胞。结果在不同处理时间，生理盐水处理组的肿瘤部位仅有少量娃像剂分布。环磷酰胺处理组存处理1h后，肿瘤部位显像剂分布少量增加；24h后，肿瘤部位显像剂分布明显增加，显影清晰。环磷酰胺处胛24h组的肿瘤／下肢比值（6．27±0．24）明显高于牛理盐水24h处理组（2．36±0．18）和环磷酰胺1h处胛组（4．00±0．38）。环磷酰胺处理24h后，TUNEL染色可见大请癌细胞凋亡。结论^99mTc—HYNIC—aflnexin Ⅴ是一种可以早期监测化疗药物治疗效果的核素捌亡显像剂，在化疗药物应用24h后就可以进行有效探测，并在注射显像剂后60min即可获得清晰的图像。Objective To evaluate if ^99mTc-HYNIC-annexin Ⅴ may be used to detect the early chemotherapeutic effect and to determine the best timing for detecting apoptosis in vivo. Methods Annexin Ⅴ was labeled with ^99mTc using HYNIC as a bifunctional agent. Normal Kumning mice received inoculation of Ehrlich ascites cells into the right upper limb. After the tumor reached 1 cm in diameter, the mice were randomly divided into saline treatment group as control and cyclophosphamide （150 mg/kg injected intraperitoneally） treatment group. ^99mTc-HYNIC-annexin Ⅴ was injected intravenously at 1h and 24 h after treatment. Region of interest technique （ROI） from the SPECT images taken at different time was used to get the ratio of tumor/limb in each group. TUNEL staining was used to detect apoptotic cells and the rates of positive stained cells were calculated. Results After treatment with saline, only little amount of the radiolabeled tracer could be seen in the tumor and showed weak image of the tumor. But after 24 h of treatment with cyelophosphamide, clear image on the tumor could be seen. 24 h after the treatment of eyclophosphamide, the ratio of tumor/limb was （6.27 ± 0.24） which was much higher than that at 24 h after treatment with saline （2.36 ± 0.18 ） and that at 1h after cyclophosphamide treatment （4. 00 ± 0.38 ）. At 24 h after cyciophosphamide treatment, TUNEL staining showed a significantly higher rate of apoptotic cells in the mice. Conclusion ^99mTc-HYNIC-annexin Ⅴ can be used as an apoptosis-imaging agent to detect and evaluate the early curative effect after chemotherapy. The effective detection of apoptotic response in tumor with ^99Tc-HYNIC-annexin Ⅴ requires a 24 h interval after chemotherapy. SPECT images can be obtained at 60 min after injection of the imaging agent. It suggests that ^99mTc-HYNIC-annexin Ⅴ may become a promising agent for apoptosis-imaging in clinical application.

关 键 词：膜联蛋白Ⅴ 凋亡 核素显像 化学疗法 

分 类 号：R686[医药卫生—骨科学]