摘要
目的探讨利用{[2-(2-氯苯基)-3-{4-[(2-18氟乙基)氧基]苯基}-5,6,7,8-四氢氧杂环庚熳并[3,2-c]吡唑-8-基]氨基}甲烷酸甲酯([^(18)F]JR-1001)作为示踪剂,通过正电子发射断层显像(PET)技术研究恐惧记忆模型鼠大脑中大麻素1型受体(CB1R)的表达变化。方法采用融合型自动合成仪制备[^(18)F]JR-1001并且进行质量检测;同时,根据恐惧记忆模型鼠建模方式进行建模。开展体外稳定性测试,采用MicroPET/CT显像和伽马计数仪对脑区摄取进行定量分析。结果经检测,合成物质为目标产物,并且符合医学使用要求。根据恐惧记忆模型鼠的检测方式,确定建模成功。进行体外稳定性得到的数据显示[^(18)F]JR-1001在体内表达稳定,并提示可通过肝脏代谢。MicroPET/CT显像及伽马计数仪数据表明实验组(恐惧记忆模型老鼠)与空白组(正常C57小鼠)在全脑各区对[^(18)F]JR-1001的摄取差异有统计学意义(P<0.05),且恐惧记忆模型鼠在多个脑区的[^(18)F]JR-1001摄取值高于正常C57小鼠。结论合成得到产品为[^(18)F]JR-1001,其质量检测、体外稳定性检测均符合医学研究要求,且MicroPET/CT显像及伽马计数仪数据提供了CB1R的PET技术为恐惧记忆疾病的早期诊断和治疗提供了新的思路和方法。本研究不仅验证了恐惧记忆与CB1R表达的关联性,还揭示了CB1R在恐惧记忆形成中的关键作用,为相关领域的研究提供了重要参考。
Objective To investigate the changes in the expression of cannabinoid type 1 receptor(CB1R)in the brains of fear memory model mice using[2-(2-chlorophenyl)-3-{4-[(2-^(18)F-fluoroethyl)oxy]phenyl}-5,6,7,8-tetrahydrooxepino[3,2-c]pyrazol-8-yl]amino]methanoic acid methyl ester([^(18)F]JR-1001)as a tracer through positron emission tomography(PET).Methods[^(18)F]JR-1001 was automatically prepared using a fused automatic synthesizer and subjected to quality control tests.Fear memory model mice were established according to established modeling protocols.In vitro stability tests were conducted,and quantitative analysis of brain region uptake was performed using MicroPET/CT imaging and a gamma counter.Results The synthesized compound was confirmed to be the target product and met medical usage requirements.Successful modeling was confirmed based on the testing methods for fear memory model mice.In vitro stability data indicated that[^(18)F]JR-1001 expressed stably in vivo and suggested hepatic metabolism.MicroPET/CT imaging and gamma counter data revealed significant differences in the uptake of[^(18)F]JR-1001 between experimental groups(fear memory model mice)and control groups(normal C57 mice)in various brain regions(P<0.05).Notably,the uptake values of[^(18)F]JR-1001 in multiple brain regions of fear memory model mice were significantly higher than those in normal C57 mice.Conclusion The synthesized product was identified as[^(18)F]JR-1001,and its quality control and in vitro stability tests met the requirements for medical research.Furthermore,data obtained from MicroPET/CT imaging and gamma counters have provided new insights and methods for the early diagnosis and treatment of fear memory disorders using PET technology targeting CB1R.Additionally,the findings of this study not only validate the correlation between fear memory and CB1R expression but also uncover the pivotal role of CB1R in the formation of fear memory,offering significant references for research in related fields.
作者
毛迪龙
魏毅
缪立威
陈俊威
曹星海
和庆钢
于聪聪
王菁
曹淑霞
豆晓锋
钟燕
金晨涛
张宏
MAO Dilong;WEI Yi;MIAO Liwei;CHEN Junwei;CAO Xinghai;HE Qinggang;YU Congcong;WANG Jing;CAO Shuxia;DOU Xiaofeng;ZHONG Yan;JIN Chentao;ZHANG Hong(School of Chemical Engineering and Biological Engineering,Zhejiang University,Hangzhou 310027,China;School of Medicine,Zhejiang University,Hangzhou 310027,China;Department of Nuclear Medicine and PET-CT Center,Second Affiliated Hospital of Zhejiang University,Hangzhou 310009,China)
出处
《分子影像学杂志》
2025年第2期131-137,共7页
Journal of Molecular Imaging
基金
国家自然科学基金委重大仪器专项(32027802)
浙江省“领雁”研发攻关计划基金项目(2022C03071,2024C03100)。
