title: Synthesis and bioevaluation of 4-chloro-2-tert-butyl-5-[2-[[1-[2-[(18) F]fluroethyl]-1H-1,2,3-triazol-4-yl]methyl]phenylmethoxy]-3(2H)-pyridazinone as potential myocardial perfusion imaging agent with PET.
abstract: This study reports the synthesis and characterization of 4-chloro-2-tert-butyl-5-[2-[[1-[2-[(18) F]fluroethyl]-1H-1,2,3-triazol-4-yl]methyl]phenylmethoxy]-3(2H)-pyridazinone ([(18) F]Fmp2) for myocardial perfusion imaging (MPI). The tosylate precursor and non-radioactive compound [(19) F]Fmp2 were synthesized and characterized by infrared, (1) H-NMR, (13) C-NMR, and mass spectra (MS). The radiotracer [(18) F]Fmp2 was obtained by one-step nucleophilic substitution of tosyl with (18) F, and evaluated as an MPI agent in vitro and in vivo. Starting from [(18) F]KF/K222 solution, the typical decay-corrected radiochemical yield (RCY) was 38 ± 8.8% with high radiochemical purity (>98%). The specific activity was calculated as 10 GBq/µmol at the end of synthesis determined by HPLC analysis. In the mice biodistribution, [(18) F]Fmp2 showed very high initial heart uptake (53.35 ± 5.47 %ID/g at 2 min after injection) and remarkable retention. The heart/liver, heart/lung, and heart/blood ratios were 7.98, 8.20, and 53.13, respectively at 2 min 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 2 h post-injection, while the heart uptake and heart/liver ratios continued to increase with time. [(18) F]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.
authors.affiliation: 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.|Department of Nuclear Medicine, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, China.
authors.forename: Tiantian
authors.initials: T
authors.lastname: Mou
authors.affiliation: Department of Nuclear Medicine, Cardiovascular Institute and Fu Wai Hospital, Chinese Academy of Medical Sciences, Beijing, 100037, China.
authors.forename: Zuoquan
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: 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.
authors.forename: Linyi
authors.initials: L
authors.lastname: You
authors.affiliation: Department of Nuclear Medicine, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Nuclear Medicine, Cardiovascular Institute and Fu Wai Hospital, Chinese Academy of Medical Sciences, Beijing, 100037, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Fang
authors.affiliation: Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing, 100875, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Lu
authors.affiliation: PET Center, Xuanwu Hospital of Capital University of Medical Sciences, Beijing, 100053, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Peng
authors.affiliation: 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.
authors.forename: Xianzhong
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000818:Animals; D005260:Female; D005462:Fluorine Radioisotopes / Q000737:chemistry*; D006321:Heart / Q000000981:diagnostic imaging*; D051379:Mice; D055414:Myocardial Perfusion Imaging / Q000379:methods*; D049268:Positron-Emission Tomography / Q000379:methods*; D011724:Pyridazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics*; D011854:Radiochemistry; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D013552:Swine; D013556:Swine, Miniature; D014018:Tissue Distribution; D014230:Triazoles / Q000138:chemical synthesis* / Q000493:pharmacokinetics*
chemical_list: C000606737:4-chloro-2-tert-butyl-5-(2-((1-(2-fluoroethyl)-1H-1,2,3-triazol-4-yl)methyl)phenylmethoxy)-3(2H)-pyridazinone; D005462:Fluorine Radioisotopes; D011724:Pyridazines; D019275:Radiopharmaceuticals; D014230:Triazoles; C428725:pyridaben
keywords: 18F-labeling; MC-I; myocardial perfusion imaging; pyridaben analog; radiopharmaceutical