1-[^(18)F]氟代乙基吲哚丙酸作为PET显像剂可行性的初步研究  

Production of 2-[18 F]-fluorobutyric acid as a PET imaging agent for prostate cancer

作　　者：董伟璇 秦开心 沈聪 施冬梅 胡文豪 段小艺[1] DONG Weixuan;QIN Kaixin;SHEN Cong;SHI Dongmei;HU Wenhao;DUAN Xiaoyi(PET/CT Center,The First Affiliated Hospital of Xi’an Jiaotong University,Xi’an 710061;Department of Nuclear Medicine,First Hospital of Shanxi Medical University,Shanxi Medical University,Taiyuan 030001,China)

机构地区：[1]西安交通大学第一附属医院PET/CT室,陕西西安710061 [2]山西医科大学第一医院核医学科,山西太原030001

出　　处：《西安交通大学学报（医学版）》2024年第6期1020-1026,共7页Journal of Xi’an Jiaotong University（Medical Sciences）

基　　金：西安交通大学横向课题资助(No.HX2022130)。

摘　　要：目的吲哚丙酸在肿瘤免疫检查点阻断治疗中有关键作用,本研究拟设计合成^(18)F-标记的吲哚丙酸即1-[^(18)F]氟代乙基-吲哚丙酸(1-[^(18)F]-IPA),并对其作为肿瘤PET显像剂进行初步研究。方法前体1-(2-对甲苯磺酸氧乙基)-吲哚丙酸甲酯与^(18)F-发生亲核取代反应,粗产品经高效液相色谱法分离纯化并收集中间体,最后水解得1-[^(18)F]-IPA。目测产品的澄清度,精密试纸测定pH值,高效液相色谱检测放射化学纯度和稳定性。ICR健康小鼠尾静脉注射1-[^(18)F]-IPA(0.2 mL,7 MBq),于5、15、25、45、75、120 min各不同时间点处死并解剖,测定1-[^(18)F]-IPA在正常小鼠体内的生物学分布;荷BxPC-3裸鼠行micro-PET/CT显像并进行图像分析。组织器官不同时间点生物学分布的比较采用Student t检验。结果1-[^(18)F]-IPA总制备时间约35~40 min,放射化学产率(45±5)%,放射化学纯度>95%。产品溶液澄清无颗粒,pH值约6.5,体内外稳定性好。于各时间点处死ICR健康小鼠并解剖后测定1-[^(18)F]-IPA在正常小鼠体内的生物学分布,结果表明除外脑组织,在ICR健康小鼠全身各主要脏器均有1-[^(18)F]-IPA的一定摄取,以肝脏、胆囊以及肾脏摄取最明显,胆囊处随时间推移放射性逐渐增高,在120 min时达到(39.86±6.56)%ID/g,骨摄取随时间无明显变化。Micro-PET/CT表明,荷BxPC-3裸鼠在注射1-[^(18)F]-IPA 30 min后的BxPC-3肿瘤处有一定量放射性摄取,但并不明显,此时最大标准摄取值(SUVmax)约为55.18±14.62。这与生物分布结果一致,脑在各时间点摄取均较低。结论1-[^(18)F]-IPA合成时间短、产率高,有望成为一种探查色氨酸吲哚代谢途径以及进一步揭示肿瘤免疫抵抗的工具。Objective In view of the crucial role of indole propionic acid in the treatment of tumor immune checkpoint blockade and further revealing its mechanism,our study intended to design and synthesize 1-[^(18)F]-fluoroethyl-indole propionic acid(1-[^(18)F]-IPA),and evaluate it as a tumor PET imaging agent.Methods The precursor 1-(2-p-toluenesulfonic acid oxygen ethyl)-methyl indole propionate underwent nucleophilic substitution reaction with^(18)F-.The crude product was separated and purified by high-performance liquid chromatography and the intermediates were collected.Finally,1-[^(18)F]-IPA was obtained by hydrolysis.The clarity of the product was measured by visual inspection,the pH value was determined by precision test paper,and the radiochemical purity and stability were determined by high-performance liquid chromatography.In order to determine the biodistribution of 1-[^(18)F]-IPA in normal mice,ICR mice were intravenously injected with 1-[^(18)F]-IPA(0.2 mL,7 MBq),and sacrificed at 5,15,25,45,75 and 120 min and dissected.Micro-PET imaging was performed and analyzed in BxPC-3 t umor-bearing nude mice.Student t test was used to compare the biodistribution of tissues and organs at different time points.Results The total preparation time of 1-[^(18)F]-IPA was 35-40 min,the radiochemical yield was(45±5)%,and the radiochemical purity was more than 95%.The product solution was clear without particles,and the pH value was 6.5,which had good stability in vitro and in vivo.The results of biodistribution in healthy ICR mice showed that except for the brain,1-[^(18)F]-IPA had a certain uptake in all major organs,with the most obvious uptake in the liver,gallbladder and kidneys.The radioactivity in the gallbladder gradually increased with time and reached(39.86±6.56)%ID/g at 120 min,but bone uptake did not change significantly with time.Micro-PET/CT showed that there was radioactive uptake at the tumor 30 min after injection of 1-[^(18)F]-IPA in Dutch BxPC-3 nude mice,but it was not obvious.At this time,SUVmax was about

关 键 词：1-[^(18)F]氟代乙基吲哚丙酸(1-[^(18)F]-IPA) 放射化学 小动物PET/CT 分子探针 

分 类 号：R817.9[医药卫生—影像医学与核医学]