Synthesis and bioevaluation of 4-chloro-2-tert-butyl-5-[2-[[1-[2-[F-18]fluroethyl]-1H-1,2,3-triazol-4-yl]methyl]phenylmethoxy]-3(2H)-pyridazinone as potential myocardial perfusion imaging agent with PET
机构：[a]Center for Molecular Imaging and Translational Medicine, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen 361005, China[b]Department of Nuclear Medicine, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China医技科室核医学科首都医科大学附属安贞医院[c]Department of Nuclear Medicine, Cardiovascular Institute and Fu Wai Hospital, Chinese Academy of Medical Sciences, Beijing 100037, China[d]Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing 100875, China[e]PET Center, Xuanwu Hospital of Capital University of Medical Sciences, Beijing 100053, China首都医科大学宣武医院
This study reports the synthesis and characterization of 4-chloro-2-tert-butyl-5-[2-[[1-[2-[F-18]fluroethyl]-1H-1,2,3-triazol-4-yl]methyl]phenylmethoxy]-3(2H)-pyridazinone ([F-18]Fmp2) for myocardial perfusion imaging (MPI). The tosylate precursor and non-radioactive compound [F-19]Fmp2 were synthesized and characterized by infrared, H-1-NMR, C-13-NMR, and mass spectra (MS). The radiotracer [F-18]Fmp2 was obtained by one-step nucleophilic substitution of tosyl with F-18, and evaluated as an MPI agent in vitro and in vivo. Starting from [F-18]KF/K-222 solution, the typical decay-corrected radiochemical yield (RCY) was 38 +/- 8.8% with high radiochemical purity (>98%). The specific activity was calculated as 10GBq/mu mol at the end of synthesis determined by HPLC analysis. In the mice biodistribution, [F-18]Fmp2 showed very high initial heart uptake (53.35 +/- 5.47 %ID/g at 2min after injection) and remarkable retention. The heart/liver, heart/lung, and heart/blood ratios were 7.98, 8.20, and 53.13, respectively at 2min post-injection. In the Positron Emission Tomography (PET) imaging study of Chinese mini-swine, the standardized uptake value of the liver decreased modestly during the 2h post-injection, while the heart uptake and heart/liver ratios continued to increase with time. [F-18]Fmp2 exhibited good stability, high heart uptake and low lung uptake in mice and Chinese mini-swine. It may be worthy of further modification to improve liver clearance for MPI in the future.
基金：
the National Natural Science Foundation of China (81471707, 81301251, 81271613)
the Fundamental Research Funds for the Central Universities (20720150063).
语种：
外文
被引次数：
WOS：
PubmedID：
中科院(CAS)分区：
出版当年[2014]版：
大类|4 区医学
小类|4 区生化研究方法4 区分析化学4 区药物化学
最新[2023]版：
大类|4 区医学
小类|4 区生化研究方法4 区分析化学4 区药物化学
JCR分区：
出版当年[2013]版：
Q3CHEMISTRY, ANALYTICALQ4CHEMISTRY, MEDICINALQ4BIOCHEMICAL RESEARCH METHODS
最新[2023]版：
Q4BIOCHEMICAL RESEARCH METHODSQ4CHEMISTRY, ANALYTICALQ4CHEMISTRY, MEDICINAL
第一作者机构：[a]Center for Molecular Imaging and Translational Medicine, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen 361005, China[b]Department of Nuclear Medicine, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China
共同第一作者：
通讯作者：
通讯机构：[a]Center for Molecular Imaging and Translational Medicine, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen 361005, China[c]Department of Nuclear Medicine, Cardiovascular Institute and Fu Wai Hospital, Chinese Academy of Medical Sciences, Beijing 100037, China[*1]School of Public Health, Xiamen University, Xiang’an South Rd., Xiang’an district, Xiamen 361102, China
推荐引用方式(GB/T 7714)：
Tiantian Mou ,Zuoquan Zhao ,Linyi You ,et al.Synthesis and bioevaluation of 4-chloro-2-tert-butyl-5-[2-[[1-[2-[F-18]fluroethyl]-1H-1,2,3-triazol-4-yl]methyl]phenylmethoxy]-3(2H)-pyridazinone as potential myocardial perfusion imaging agent with PET[J].JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS.2015,58(8):349-354.doi:10.1002/jlcr.3310.
APA：
Tiantian Mou,,Zuoquan Zhao,,Linyi You,,Qian Wang,,Wei Fang,...&Xianzhong Zhang.(2015).Synthesis and bioevaluation of 4-chloro-2-tert-butyl-5-[2-[[1-[2-[F-18]fluroethyl]-1H-1,2,3-triazol-4-yl]methyl]phenylmethoxy]-3(2H)-pyridazinone as potential myocardial perfusion imaging agent with PET.JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS,58,(8)
MLA：
Tiantian Mou,,et al."Synthesis and bioevaluation of 4-chloro-2-tert-butyl-5-[2-[[1-[2-[F-18]fluroethyl]-1H-1,2,3-triazol-4-yl]methyl]phenylmethoxy]-3(2H)-pyridazinone as potential myocardial perfusion imaging agent with PET".JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS 58..8(2015):349-354
