摘要
目的探讨2-[18F]-A-85380的合成及在小鼠体内分布。方法以Me3N+-Boc-A-85380、CF3S03-为反应前体,在含氮芳香环的2位用18F进行标记,合成nAChRs显像剂2[-18F]-A-85380;以聚酰胺薄膜为支持介质、生理盐水为展开剂,测定标记物的标记率和放化纯度;KM小鼠尾静脉注射0.5 mL(1.295 MBq)2[-18F]-A-85380,分别在5、15、30、60、90、120、150、180 min处死。取血、心、肝、脾、肺、肾、胃、小肠、膀胱、甲状腺、颌下腺、脑、肌肉、大肠、骨骼,测其质量及放射性计数,计算%ID/g。结果2[-18F]-A-85380的标记率达93%,其放化纯在标记后2、4、6 h均大于90%。药物分布结果显示,2[-18F]-A-85380在小鼠体内广泛分布,主要经过肝脏和肾脏进行代谢。肝、肾的放射性摄取在注入后5 min时分别为0.289%ID/g、0.590%ID/g,180 min时则分别下降为0.024%ID/g、0.016%ID/g,血液中放射性清除较快,注入后5 min时血液中放射性摄取为0.093%ID/g,180 min时为0.002%ID/g。注入后60 min脑中的放射性摄取达到最高值为0.145%ID/g,150 min时脑内摄取大于其他组织器官,脑中摄取较多、清除缓慢、状态稳定,脑中分布达稳定状态的时间大于180 min。胃和颌下腺中摄取也较多,膀胱辐射吸收剂量最高。结论2[-18F]-A-85380制备方便,体外稳定,体内主要经过肝、肾代谢,脑内分布较多且状态稳定,可用于进一步的烟碱受体显像研究。
Objective To investigate the radiosynthesis of 2-[18F]-A-85380 and its biodistribution in mice.Methods 2-[18F]-A-85380 was synthesized with Me3N ＋-Boc-A-85380.CF3S03-as precursor,using 18F labeled the nitrogen-containing aromatic ring.The radiolabeled compound was characterized by polymide TLC,in which the substratum of saline was used as developing agent to measure the radiochemical purity and labeling yield.KM mice were sacrificed at 5,15,30 60,90,120 150,180 min after tail vein injection of 0.5 mL（1.295MBq）freshly prepared 2-[18E]-A-85380.Samples of blood,heart,hver,spleen,lung,kidney,stomach,small intestine,bladder,thyroid,submandibular gland,brain,muscle,large intestine and bone were taken,weighed and gamma counts were measured.The percent of injected dose per gram （％ID/g） was calculated for each sample.Results The labeling yield of 2-[18F]-A-85380 was 93％ and its radiochemical purity exceeded 90％ at 2,4 and 6 h.Biodistribution in mice demonstrated that 2-[18F]-A-85380 was extensive in mice,and it was metabolized mainly in liver and kidney,as indicated by their uptake of 0.289％ ID/g and 0.590％ ID/g at 5 min dropping to 0.024％ ID/g and 0.016％ ID/g at 180 min,respectively.The brain uptake of 2-[18F]-A-85380 in mice reached a maximum of 0.145％ ID/g at 60 min after injection.And the uptake of brain exceeded the other organs at 150 min after injection,with the most uptake,the slowest elimination and stable state.The stability of brain distribution needed more than 180 min.The distribution of stomach and submandibular gland were relative high as well.Bladder wall received the highest radiation dose.Conclusion The preparation of 2-[18F]-A-85380 is convenient and stable and it is metabolized mainly in liver and kidney and exhibits a relative high uptake and stable state in brain,which is worthy of further studying for nAChRs imaging.
出处
《中国医科大学学报》
CAS
CSCD
北大核心
2013年第9期777-780,共4页
Journal of China Medical University
基金
国家自然科学基金(81000623)
