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《国际放射医学核医学杂志》[ISSN:1673-4114/CN:12-1381/R]

卷:

期数:

2018年第6期

页码:

524-529

栏目:

基础研究

出版日期:

2018-12-31

文章信息/Info

Title:

Automated synthesis and biodistribution study of cardiac fatty acid metabolism imaging agent ¹⁸F-FTHA

作者:

何玉林¹; 2;  张晓军²;  李剑波¹;  张国建¹;  张锦明²;  王雪梅¹

1. 010050 呼和浩特, 内蒙古医科大学附属医院核医学科;
2. 100853 北京, 解放军总医院核医学科

Author(s):

He Yulin¹; 2;  Zhang Xiaojun²;  Li Jianbo¹;  Zhang Guojian¹;  Zhang Jinming²;  Wang Xuemei¹

1. Department of Nuclear Medicine, Affiliated Hospital of Inner Mongolia Medical University, Hohhot 010050, China;
2. Department of Nuclear Medicine, the PLA General Hospital, Beijing 100853, China

关键词:

心肌代谢; 脂肪酸; 正电子发射断层显像术; 14(R; S)-[¹⁸F]-氟-6-硫杂十七烷酸; 生物学分布

Keywords:

Cardiac metabolism; Fatty acid; Positron emission tomography; 14(R; S)-[¹⁸F]fluoro-6-thia-heptadecanoic acid; Biodistribution

DOI:

10.3760/cma.j.issn.1673-4114.2018.06.009

摘要:

目的 实现心肌脂肪酸代谢显像剂14（R，S）-[¹⁸F]-氟-6-硫杂十七烷酸（¹⁸F-FTHA）的全自动化合成，并评价其在正常昆明小鼠体内的生物学分布特征。方法 采用自动化合成模块以苄基-14-（R，S）-对甲苯磺酰基-6-硫代十七烷酸脂为前体合成¹⁸F-FTHA。并对其物理（性状、放射性活度、比活度、半衰期和放射性核纯度）、化学（化学纯度、放射化学纯度和室温稳定性）和生物学（毒性、无菌和细菌内毒素）性能进行鉴定。昆明小鼠20只，采用随机数字表法分为4组（每组5只），经小鼠尾部静脉分别注射¹⁸F-FTHA显像剂7.4 MBq（体积<0.2 mL），注射后15、30、60、90 min时各处死1组，分别取心脏、肝脏、脾、肺、肾脏、肌肉和骨等主要器官和血液，称重并测定放射性计数，计算每克组织百分注射剂量率（%ID/g）。组间数据比较采用配对t检验。结果 合成时间约50 min，合成产率为（10.0±1.7）%。¹⁸F-FTHA注射液为含10%乙醇的无菌、无内毒素、无色澄清透明溶液，pH值为6～7，比活度为65 GBq/mmol，放射性核纯度≥99%，放化纯度>98%。正常昆明小鼠体内生物学分布实验结果显示，¹⁸F-FTHA在血液中清除快，心肌摄取高，非靶器官摄取较低。在注射显像剂后60 min时，心肌、肺和肝脏的放射性摄取分别为（19.04±4.87）%ID/g、（3.05±0.52）%ID/g和（5.99±2.96）%ID/g，心肌与肺的摄取比值为6/1（t=0.27，P=0.01），心肌与肝脏的摄取比值为3/1（t=0.75，P=0.02），差异均有统计学意义；肝脏摄取呈先高后低的趋势，在15 min和30 min时肝脏摄取略高于心肌摄取。结论 实现了¹⁸F-FTHA的自动化合成，其放化纯度高，稳定性好。物理、化学和生物学鉴定结果证实其安全可靠，小鼠体内生物学分布实验证实其心肌摄取高于非靶器官，可用于实验研究。

Abstract:

Objective To achieve the fully automated synthesis of myocardial fatty acid metabolism imaging agent 14(R, S)-[¹⁸F]fluoro-6-thia-heptadecanoic acid (¹⁸F-FTHA), its biological distribution characteristics in normal Kunming mice were evaluated. Methods An automated synthesis module benzyl-14-tosyloxy-6-thia-heptadecanoate was used as precursor. The synthesis process was completed in four steps:nucleophilic substitution, alkaline hydrolysis, semi-preparative high-performance liquid chromatography, and solid-phase extraction. The physical(traits, activity, specific activity, half-life, and radionuclide purity), chemical (chemical purity, radiochemical purity, and room temperature stability), and biological properties (toxicity, sterility, and bacterial endotoxin) of the compound were identified. Twenty Kunming mice were randomly divided into four groups, with five mice in each group. The imaging agent ¹⁸F-FTHA 7.4 MBq(volume<0.2 mL) was injected through the tail vein. A group of mice was sacrificed at 15, 30, 60, and 90 min after injection, and the blood and main organs, such as heart, liver, spleen, lung, kidney, muscle, and bone, were obtained and weighed. The radioactivity count was measured by a gamma counter. The radioactive uptake(%ID/g) was calculated. Results The total synthesis time was about 50 min. The synthetic yield was(10.0±1.7)%. The ¹⁸F-FTHA is an injection containing 10% ethanol. The compound is a sterile, endotoxin-free, colorless clear solution. Its pH value is 6-7, specific activity is 65 GBq/mmol, radioactive nuclear purity is ≥ 99%, and radiochemical purity is > 98%, which remained at > 95% after 6 h at room temperature. Biodistribution experiments in normal Kunming mice showed that ¹⁸F-FTHA rapidly cleared in the blood, and a high myocardial uptake and low non-target organ uptake were observed. At 60 min after injection, the radioactivity uptake of myocardium, lungs, and liver reached(19.04±4.87)%ID/g, (3.05±0.52)%ID/g and(5.99±2.96)%ID/g, respectively. The heart-to-lung and heart-to-liver uptake ratios totaled 6/1 and 3/1, respectively. The liver uptake at 15 and 30 min was slightly higher than the myocardial uptake. Conclusions The synthesis of ¹⁸F-FTHA, which features high radiochemical purity and good stability, has been automatically completed. Physical, chemical, and biological property identification results confirmed that the compound is safe and reliable. The biological distribution experiments on mice confirmed that myocardial uptake was higher than that of non-target organs. Thus, ¹⁸F-FTHA is suitable for experimental research.

备注/Memo

备注/Memo:

收稿日期:2018-07-04。
基金项目:国家自然科学基金（81660295）；内蒙古自治区自然科学基金（2016MS（LH）0812）
通讯作者:何玉林,Email:hyl-0215@163.com

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更新日期/Last Update: 2018-12-31