机构：[a]Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University, 19 Xinjiekou Outer St., Beijing 100875, China[b]Department of Nuclear Medicine, Cardiovascular Institute and Fu Wai Hospital, Chinese Academy of Medical Sciences, Beijing 100037, China[c]PET Center of Xuan Wu Hospital, Capital Medical University, Beijing 100053, China首都医科大学宣武医院
Myocardial extractions of pyridaben, a mitochondrial complex I (MC-I) inhibitor, is well correlated with blood flow. Based on the synthesis and characterization of pyridaben analogue 2-tert-butyl-5-[2-(2-[F-18]fluroethoxy)ethoxy]benzyloxy]-4-chloro-2H-pyridazin-3-one ([F-18]FP2OP), this study assessed its potential to be developed as myocardial perfusion imaging (MPI) agent. Methods: The tosylate labeling precursor 2-(2-(4-(tert-butyl-5-chloro-6-oxo-1,6-dihydro-pyridazin-4-yloxymethyl)benzyloxy)ethoxy) ethyl ester (OTs-P2OP) and the nonradioactive 2-tert-butyl-5-[2-(2-[F-19]fluroethoxy)ethoxy]benzyloxy]-4-chloro-2H-pyridazin-3-one ([F-19]FP2OP) were synthesized and characterized by IR, H-1 NMR, C-13 NMR and MS analysis. By substituting tosyl of precursor OTs-P2OP with F-18, the radiolabeled complex [F-18]FP2OP was prepared and further evaluated for its in vitro physicochemical properties, in vivo biodistribution, the metabolic stability in mice, ex vivo autoradiography and cardiac PET/CT imaging. Results: Starting with [F-18]F Kryptofix 2.2.2./K2CO3 solution, the total reaction time for [F-18]FP2OP was about 100 min, with final high-performance liquid chromatography purification included. Typical decay-corrected radiochemical yield stayed at 41 +/- 5.3%, the radiochemical purity, 98% or more. Biodistribution in mice showed that the heart uptake of [F-18]FP2OP was 41.90 +/- 4.52% ID/g at 2 min post-injection time, when the ratio of heart/liver, heart/lung and heart/blood reached 6.83, 9.49 and 35.74, respectively. Lipophilic molecule was further produced by metabolized [F-18]FP2OP in blood and urine at 30 min. Ex vivo autoradiography demonstrates that [F-18]FP2OP may have high affinity with MC-I and that can be blocked by [F-19] FP2OP or rotenone (a known MC-I inhibitor). Cardiac PET images were obtained in a Chinese mini-swine at 5, 15, 30 and 60 min post-injection time with high quality. Conclusion: [F-18]FP2OP was synthesized with high radiochemical yield. The promising biological properties of [F-18]FP2OP suggest high potential as MPI agent for positron emission tomography in the future. (C) 2009 Elsevier Ltd. All rights reserved.
基金：
the National Natural Science Foundation of China (20871020) and 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, 19 Xinjiekou Outer St., Beijing 100875, China
通讯作者：
通讯机构：[a]Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University, 19 Xinjiekou Outer St., Beijing 100875, China
推荐引用方式(GB/T 7714)：
Tiantian Mou,Huihui Jing,Wenjiang Yang,et al.Preparation and biodistribution of [F-18]FP2OP as myocardial perfusion imaging agent for positron emission tomography[J].BIOORGANIC & MEDICINAL CHEMISTRY.2010,18(3):1312-1320.doi:10.1016/j.bmc.2009.12.022.
APA：
Tiantian Mou,Huihui Jing,Wenjiang Yang,Wei Fang,Cheng Peng...&Yunchuan Ma.(2010).Preparation and biodistribution of [F-18]FP2OP as myocardial perfusion imaging agent for positron emission tomography.BIOORGANIC & MEDICINAL CHEMISTRY,18,(3)
MLA：
Tiantian Mou,et al."Preparation and biodistribution of [F-18]FP2OP as myocardial perfusion imaging agent for positron emission tomography".BIOORGANIC & MEDICINAL CHEMISTRY 18..3(2010):1312-1320
