心肌脂肪酸代谢显像剂18F-FTHA的自动化合成与生物学分布研究  

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] He Yulin;Zhang Xiaojun;Li Jianbo;Zhang Guojian;Zhang Jinming;Wang Xuemei(Department of Nuclear Medicine, Affiliated Hospital of Inner Mongolia Medical University, Hohhot 010050, China;Department of Nuclear Medicine, the PLA General Hospital, Beijing 100853, China)

机构地区：[1]内蒙古医科大学附属医院核医学科,呼和浩特 010050 [2]解放军总医院核医学科,北京100853

出　　处：《国际放射医学核医学杂志》2018年第6期524-529,共6页International Journal of Radiation Medicine and Nuclear Medicine

基　　金：国家自然科学基金(81660295);内蒙古自治区自然科学基金(2016MS(LH)0812).

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7.4MBq(体积<0.2mL),注射后15、30、60、90min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50min,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65GBq/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60min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15min和30min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。ObjectiveTo 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.MethodsAn 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.ResultsThe 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 u

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 

分 类 号：R817[医药卫生—影像医学与核医学]