Monitoring Apoptosis of Breast Cancer Xenograft After Paclitaxel Treatment With 99mTc-Labeled Duramycin SPECT/CT.
Monitoring Apoptosis of Breast Cancer Xenograft After Paclitaxel Treatment With 99mTc-Labeled Duramycin SPECT/CT.
复制标题
用 99mTc 标记的耐久霉素 SPECT/CT 监测紫杉醇治疗后乳腺癌异种移植物的细胞凋亡
DOI：
10.1177/1536012115624918
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发表时间：
2016
影响因子：
2.8
通讯作者：
Wang F
中科院分区：
文献类型：
--
作者：
Luo R;Niu L;Qiu F;Fang W;Fu T;Zhao M;Zhang YJ;Hua ZC;Li XF;Wang F
我们的目的是验证99mTc-duramycin作为一种潜在的细胞凋亡探针，用于监测乳腺癌异种移植肿瘤对紫杉醇的反应的可行性。利用紫杉醇处理的人乳腺癌MDA-MB-231细胞，体外验证了99mTc-duramycin与磷脂酰乙醇胺的结合。雌性BALB/c小鼠（n = 5）携带乳腺癌异种移植物，随机分为2组，分别腹腔注射紫杉醇或磷酸盐缓冲盐水40 mg/kg。治疗后72小时注射99mTc-duramycin (37-55.5 MBq)，注射后2小时进行单光子发射计算机断层扫描/计算机断层扫描。用流式细胞术检测肿瘤组织的凋亡细胞和活化的caspase 3。光镜和透射电镜观察细胞超微结构变化。放射化学纯度为90%的99mTc-duramycin表现出快速的血液清除和主要的肾脏清除。紫杉醇治疗组肿瘤与肌肉之比（5.29±0.62）显著高于对照组。紫杉醇治疗后，肿瘤体积显著减小，99mTc-duramycin（离体）摄食量显著增加，这与凋亡指数、组织学和超微结构变化一致。我们的数据证明了99mTc-duramycin在紫杉醇化疗后早期检测乳腺癌异种移植后细胞凋亡的可行性。
Our goal was to validate the feasibility of 99mTc-duramycin as a potential apoptosis probe for monitoring tumor response to paclitaxel in breast cancer xenografts. The binding of 99mTc-duramycin to phosphatidylethanolamine was validated in vitro using paclitaxel-treated human breast carcinoma MDA-MB-231 cells. Female BALB/c mice (n = 5) bearing breast cancer xenografts were randomized into 2 groups and intraperitoneally injected with 40 mg/kg paclitaxel or phosphate-buffered saline. 99mTc-duramycin (37-55.5 MBq) was injected at 72 hours posttreatment, and single-photon emission computed tomography/computed tomography was performed at 2 hours postinjection. Apoptotic cells and activated caspase 3 in explanted tumor tissue were measured by flow cytometry. Cellular ultrastructural changes were assessed by light and transmission electron microscopy. 99mTc-duramycin with radiochemical purity of 90% exhibited rapid blood clearance and predominantly renal clearance. The tumor-to-muscle ratio in the paclitaxel-treated group (5.29 ± 0.62) was significantly higher than that in the control. Tumor volume was decreased dramatically, whereas tumor uptake of 99mTc-duramycin (ex vivo) significantly increased following paclitaxel treatment, which was consistent with apoptotic index, histological findings, and ultrastructural changes. Our data demonstrated the feasibility of 99mTc-duramycin for early detection of apoptosis after paclitaxel chemotherapy in breast carcinoma xenografts.