靶向单羧酸转运蛋白分子探针[18F]FEtO-CHC的制备与初步显像  

Preparation and Preliminary Imaging Study of Molecular Probe[18F]FEtO-CHC Targeting Monocarboxylic Acid Transporter

作　　者：王红亮[1] 杨柳[1] 赵琦南 秦开心 施冬梅 郑钰州 WANG Hong-liang;YANG Liu;ZHAO Qi-nan;QIN Kai-xin;SHI Dong-mei;ZHENG Yu-zhou(Department of Nuclear Medicine,First Hospital of Shanxi Medical University,Shanxi Medical University,Taiyuan 030001,China)

机构地区：[1]山西医科大学第一医院核医学科,山西太原030001

出　　处：《核化学与放射化学》2023年第3期259-266,I0004,共9页Journal of Nuclear and Radiochemistry

基　　金：国家自然科学基金资助项目(81471695)。

摘　　要：以单羧酸转运体(monocarboxylic acid transporters,MCTs)的小分子抑制剂α-氰基-4-羟基-肉桂酸(α-cyano-4-hydroxy-cinnamic acid,CHC)为先导化合物,设计合成了新型18 F标记的氟乙氧基修饰的α-氰基-4-羟基-肉桂酸探针([18F]FEtO-CHC),并对其进行了初步的体内外稳定性和肿瘤PET/CT显像研究。以α-氰基-4-(2-对甲苯磺酰氧乙氧基)-肉桂酸甲酯为前体化合物,经与18F-进行亲核反应得到中间体化合物α-氰基-4-(2-[18F]-氟乙氧基)-肉桂酸甲酯([18F]4),经过高效液相色谱分离纯化,中间体[18F]4经2 mol/L NaOH溶液水解后用1 mol/L HCl溶液中和,得到α-氰基-4-(2-[18 F]-氟乙氧基)-肉桂酸([18F]FEtO-CHC,[18F]5)。细胞增殖抑制实验结果表明,化合物[19F]5较CHC具有更好的细胞增殖的抑制活性。[18F]5表现出较好的体内外稳定性和生物安全性,并且DU145前列腺癌荷瘤小鼠Micro-PET/CT显像显示[18F]5在肿瘤处具有明显的放射性浓聚特征。[18F]FEtO-CHC具有合成过程简单、稳定性好、生物安全性高,且具有肿瘤PET显像能力,是一种潜在可靶向MCTs的小分子PET显像剂。Usingα-cyano-4-hydroxy-cinnamic acid,a small molecule inhibitor of monocarboxylic acid transporters(MCTs),as the lead compound,a novel 18 F-labeledα-cyano-4-hydroxy-cinnamic acid probe was designed and synthesized.The preliminary evaluation of stability and tumor PET/CT imaging were performed in this study.Takingα-cyano-4-(2-p-toluenesulfonyl-ethoxy)-methyl cinnamate as the precursor compound,the intermediate compoundα-cyano-4-(2-[18F]-fluoroethoxy)-methyl cinnamate([18 F]4)was obtained by nucleophilic reaction with 18 F-,which was separated and purified by high performance liquid chromatography(HPLC).α-cyano-4-(2-[18 F]-fluoroethoxy)-cinnamic acid([18F]FEtO-CHC,[18F]5)can be obtained from the hydrolysis of[18 F]4 with 2 mol/L NaOH solution and the neutralization with 1 mol/L HCl solution.The results of cell proliferation inhibition assay show that compound[19 F]5 has better inhibitory activity than that of CHC.[18F]FEtO-CHC shows good stability and biosafety from the in vitro and in vivo studies,and micro-PET/CT imaging in DU145 prostate cancer tumor-bearing mice shows that[18 F]5 has obvious radioactive accumulation at the tumor site.[18F]FEtO-CHC has the advantages of simple synthesis process,good stability,high biological safety,and ability for tumor PET imaging.It is a potential PET agent for specific MCTs imaging.

关 键 词：单羧酸转运蛋白 代谢共生 α-氰基-4-羟基-肉桂酸 PET显像探针 放射化学合成 

分 类 号：R817.9[医药卫生—影像医学与核医学]