18F-ML-10 PET/CT成像早期评价阿霉素诱导的心脏毒性

中华核医学与分子影像杂志 Pub Date : 2019-10-25 DOI:10.3760/CMA.J.ISSN.2095-2848.2019.10.002

Q. Shi, Yuyun Sun, Sheng Cao, Jian Zhang, J. Zhan, Yongping Zhang, Shaoli Song, YingJian Zhang, Mingwei Wang

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All mice were subjected to 18F-fluorodeoxyglucose (FDG) and 18F-ML-10 PET/CT imaging at day 0, 2, 9, 16, and left ventricular ejection fraction (LVEF) was continuously monitored using cine cardiac MR (cine-CMR) imaging. The region of interest (ROI) was delineated on PET/CT images, and the maximum percentage activity of injection dose per gram of tissue (%ID/g) was calculated. The mice were sacrificed after imaging, and the heart tissue was taken for HE staining and TdT-mediated dUTP nick end labeling (TUNEL) assay. One-way analysis of variance, independent-samples t test and Pearson correlation analysis were used to analyze the data. \n \n \nResults \nIn the chemotherapy group, the myocardial 18F-FDG uptake on day 0, 2, 9, 16 were (63.3±14.5), (93.7±24.0), (153.6±20.6) and (135.8±32.5) %ID/g respectively, and 18F-ML-10 uptake were (0.09±0.02), (0.18±0.03), (0.22±0.04) and (0.55±0.12) %ID/g respectively. 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引用次数: 0

摘要

目的探讨2-（5-[18F]氟戊基）-2-甲基丙二酸（18F-ML-10）PET/CT细胞凋亡分子成像早期监测阿霉素（DOX）心脏毒性的可行性。方法将47只BALB/c小鼠按随机数表随机分为化疗组（n=30）和对照组（n=17）。化疗组小鼠每周腹膜内注射DOX（4mg/kg）一次，持续3周，对照组小鼠注射等量生理盐水。所有小鼠在第0、2、9、16天接受18F-氟脱氧葡萄糖（FDG）和18F-ML-10 PET/CT成像，并使用电影心脏MR（电影CMR）成像连续监测左心室射血分数（LVEF）。在PET/CT图像上描绘感兴趣区域（ROI），并计算每克组织注射剂量的最大活性百分比（%ID/g）。成像后处死小鼠，取心脏组织进行HE染色和TdT介导的dUTP缺口末端标记（TUNEL）测定。采用单因素方差分析、独立样本t检验和Pearson相关分析对数据进行分析。结果化疗组第0、2、9、16天心肌18F-FDG摄取量分别为（63.3±14.5）、（93.7±24.0）、（153.6±20.6）和（135.8±32.5）%ID/g，18F-ML-10摄取量分别是（0.09±0.02）、（0.18±0.03）、（0.22±0.04）和（0.55±0.12）%ID/g。与基线（第0天）相比，化疗组在DOX给药后各时间点的18F-FDG和18F-ML-10摄取量均显著增加（F=6.823，20.848，均P 0.05）。TUNEL和HE染色显示化疗组心肌细胞明显凋亡和空泡化，细胞凋亡指数（AI）与18F-ML-10摄取呈正相关（r=0.950，P<0.01）。电影CMR成像结果显示，化疗组在DOX给药后LVEF持续下降（F=4.507，P<0.05），18F-ML-10摄取量与LVEF呈显著负相关（r=-0.709，P=0.01）。鉴于18F-ML-10的高靶向特异性，在心脏毒性的早期评估中，它可能比18F-FDG具有更大的临床转化优势。关键词：心脏毒性；阿霉素；正电子发射断层扫描；层析成像，X射线计算机；老鼠

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18F-ML-10 PET/CT imaging in early evaluation of doxorubicin-induced cardiotoxicity

Objective To investigate the feasibility of early monitoring doxorubicin (DOX)-induced cardiotoxicity by apoptosis molecular imaging of 2-(5-[18F]fluoro-pentyl)-2-methyl-malonic acid (18F-ML-10) PET/CT. Methods Forty-seven BALB/c mice were randomly divided into the chemotherapy group (n=30) and the control group (n=17) according to the random number table. The mice in chemotherapy group were intraperitoneally injected with DOX (4 mg/kg) once a week for 3 weeks and mice in the control group were injected with the same amount of normal saline. All mice were subjected to 18F-fluorodeoxyglucose (FDG) and 18F-ML-10 PET/CT imaging at day 0, 2, 9, 16, and left ventricular ejection fraction (LVEF) was continuously monitored using cine cardiac MR (cine-CMR) imaging. The region of interest (ROI) was delineated on PET/CT images, and the maximum percentage activity of injection dose per gram of tissue (%ID/g) was calculated. The mice were sacrificed after imaging, and the heart tissue was taken for HE staining and TdT-mediated dUTP nick end labeling (TUNEL) assay. One-way analysis of variance, independent-samples t test and Pearson correlation analysis were used to analyze the data. Results In the chemotherapy group, the myocardial 18F-FDG uptake on day 0, 2, 9, 16 were (63.3±14.5), (93.7±24.0), (153.6±20.6) and (135.8±32.5) %ID/g respectively, and 18F-ML-10 uptake were (0.09±0.02), (0.18±0.03), (0.22±0.04) and (0.55±0.12) %ID/g respectively. Compared with baseline (day 0), 18F-FDG and 18F-ML-10 uptake were significantly increased in the chemotherapy group at each time point after DOX administration(F=6.823, 20.848, both P 0.05). TUNEL and HE staining indicated that the cardiomyocytes in the chemotherapy group showed obvious apoptosis and vacuolization, and the apoptotic index (AI) was positively correlated with the 18F-ML-10 uptake (r=0.950, P<0.01). The cine-CMR imaging results showed that the LVEF in the chemotherapy group continued to decrease after DOX administration (F=4.507, P<0.05), and significant difference was identified at day 16 (t=2.980, P<0.05). There was a significant negative correlation between 18F-ML-10 uptake and LVEF (r=-0.709, P=0.01). Conclusions Both 18F-FDG and 18F-ML-10 PET/CT imaging can early assess DOX-induced cardiotoxicity in vivo. Given the high targeting specificity of 18F-ML-10, it may have a greater clinical transformation advantage over 18F-FDG in early assessment of cardiotoxicity. Key words: Cardiotoxicity; Doxorubicin; Positron-emission tomography; Tomography, X-ray computed; Mice

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来源期刊

中华核医学与分子影像杂志核医学，分子影像

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期刊介绍： Chinese Journal of Nuclear Medicine and Molecular Imaging (CJNMMI) was established in 1981, with the name of Chinese Journal of Nuclear Medicine, and renamed in 2012. As the specialized periodical in the domain of nuclear medicine in China, the aim of Chinese Journal of Nuclear Medicine and Molecular Imaging is to develop nuclear medicine sciences, push forward nuclear medicine education and basic construction, foster qualified personnel training and academic exchanges, and popularize related knowledge and raising public awareness. Topics of interest for Chinese Journal of Nuclear Medicine and Molecular Imaging include: -Research and commentary on nuclear medicine and molecular imaging with significant implications for disease diagnosis and treatment -Investigative studies of heart, brain imaging and tumor positioning -Perspectives and reviews on research topics that discuss the implications of findings from the basic science and clinical practice of nuclear medicine and molecular imaging - Nuclear medicine education and personnel training - Topics of interest for nuclear medicine and molecular imaging include subject coverage diseases such as cardiovascular diseases, cancer, Alzheimer’s disease, and Parkinson’s disease, and also radionuclide therapy, radiomics, molecular probes and related translational research.