机构：[a]Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing 100875, China[b]Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen 361005, China[c]PET Center of Xuan Wu Hospital, Capital Medical University, Beijing 100053, China首都医科大学宣武医院[d]Department of Nuclear Medicine, Cardiovascular Institute and Fu Wai Hospital, Chinese Academy of Medical Sciences, Beijing 100037, China
Introduction: Cardiac myosin is a potential molecular target for heart failure imaging since its changes can be used to assess the function of heart. In this study, two analogues of Omecamtiv Mecarbil, which is the first selective activator of cardiac myosin, were synthesized and radio-labeled with F-18. Then the radio-compounds were evaluated as potential cardiac myosin imaging agent. Methods: The labeling precursor and the nonradioactive compounds were synthesized and characterized by IR, H-1 NMR, C-13 NMR and MS analysis. By substituting bromo of precursors with F-18, the radiolabeled compounds [F-18]8 and [F-18]10 were prepared and further evaluated for their in vitro physicochemical properties, stabilities, protein binding assay and ex vivo biodistribution. Results: Starting with [F-18]F- Kryptofix 2.2.2./K2CO3 solution, the total reaction time for [F-18]8 and [F-18]10 was about 40 min respectively, with final high-performance liquid chromatography purification included. Typical decay-corrected radiochemical yield stayed at 12.47% +/- 3.30% (n = 8), the radiochemical purity, 98% or more. Their specific activity was estimated as 50 GBq/mu mol. Both [F-18]8 and [F-18]10 could be stable after incubation in water at room temperature and in serum or binding buffer at 37 degrees C for 3 h. Biodistribution in normal mice showed that both [F-18]8 and [F-18]10 have good heart uptake at 2 min post-injection time. Compound [F-18]10 has better heart retention and higher heart to background ratios than those of [F-18]8. In vitro protein binding assay demonstrates that [F-18]10 may have high affinity with myosin from bovine heart. Conclusion: [F-18]8 and [F-18]10 were synthesized with good radiochemical yield and high radiochemical purity (>98%). One of the compounds ([F-18]10) has higher bovine heart myosin binding affinity and better heart/liver ratio. It will be further evaluated as a potent cardiac myosin imaging agent in normal and systolic heart failure model with positron emission tomography in the future. (C) 2013 Elsevier Inc. All rights reserved.
基金：
National Natural Science Foundation of China [21271030, 20871020]; Fundamental Research Funds for the Central Universities of China; Beijing Natural Science Foundation [2092018]
第一作者机构：[a]Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing 100875, China
通讯作者：
通讯机构：[*1]Center for Molecular Imaging and Translational Medicine, 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)：
Mingru Zhang,Tiantian Mou,Zuoquan Zhao,et al.Synthesis and F-18-labeling of the analogues of Omecamtiv Mecarbil as a potential cardiac myosin imaging agent with PET[J].NUCLEAR MEDICINE AND BIOLOGY.2013,40(5):689-696.doi:10.1016/j.nucmedbio.2013.02.013.
APA：
Mingru Zhang,Tiantian Mou,Zuoquan Zhao,Cheng Peng,Yunchuan Ma...&Xianzhong Zhang.(2013).Synthesis and F-18-labeling of the analogues of Omecamtiv Mecarbil as a potential cardiac myosin imaging agent with PET.NUCLEAR MEDICINE AND BIOLOGY,40,(5)
MLA：
Mingru Zhang,et al."Synthesis and F-18-labeling of the analogues of Omecamtiv Mecarbil as a potential cardiac myosin imaging agent with PET".NUCLEAR MEDICINE AND BIOLOGY 40..5(2013):689-696
