title: Synthesis and Bio-Evaluation of New (18) F-Labeled Pyridaben Analogs with Improved Stability for Myocardial Perfusion Imaging in Mice.
abstract: To improve the stability of (18) F-labeled pyridaben analogs for myocardial perfusion imaging, three new analogs of pyridaben ([(18) F]FPTP2, [(18) F]FPTP-P2, and [(18) F]FPTP-P3) were synthesized with 'side chain' modifications. The radiolabeled tracers and corresponding non-radioactive compounds were obtained by substituting tosyl group with (18/19) F. The effect of structure modification on myocardial targeting and physicochemical properties of new tracers were evaluated in vitro and in vivo. The total radiosynthesis time of these tracers was approximately 70-90 min with high decay-corrected radiochemical yields (36-65%) and good radiochemical purity (> 98%). These lipophilic tracers exhibited obvious improved stability in water. Studies of their biodistribution in normal Kunming mice demonstrated that [(18) F]FPTP2 exhibited very high initial heart uptake (39.70 ± 2.81 %ID/g at 2 min after injection) and low background in the liver, blood, and soft tissues. The heart-to-liver, heart-to-lung, and heart-to-blood ratios were 3.59, 19.34, and 67.34 at 15 min postinjection, respectively. Favorable myocardial targeting property and remarkable improvement of stability of [(18) F]FPTP2 suggest that the substitution of the phenyl 'sidechain' with other non-phenyl rings has no effect on the myocardial targeting property of (18) F-labeled pyridaben analogs.
authors.affiliation: Department of Nuclear Medicine, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, China.|Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing, 100875, China.
authors.forename: Tiantian
authors.initials: T
authors.lastname: Mou
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, 361102, China.|Department of Nuclear Medicine, Cardiovascular Institute and Fuwai Hospital, Chinese Academy of Medical Sciences, Beijing, 100037, China.
authors.forename: Zuoquan
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing, 100875, China.|Center for Molecular Imaging and Translational Medicine, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen, 361102, China.
authors.forename: Pu
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Department of Nuclear Medicine, Cardiovascular Institute and Fuwai Hospital, Chinese Academy of Medical Sciences, Beijing, 100037, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Fang
authors.affiliation: Beijing PET Center of Xuanwu Hospital, Capital Medical University, Beijing, 100053, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Peng
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: Department of Nuclear Medicine, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Beijing PET Center of Xuanwu Hospital, Capital Medical University, Beijing, 100053, China.
authors.forename: Yunchuan
authors.initials: Y
authors.lastname: Ma
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, 361102, China.
authors.forename: Xianzhong
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000818:Animals; D005260:Female; D005462:Fluorine Radioisotopes / Q000737:chemistry*; D008297:Male; D051379:Mice; D055414:Myocardial Perfusion Imaging / Q000379:methods*; D011724:Pyridazines / Q000032:analysis / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D011877:Radionuclide Imaging / Q000379:methods; D019275:Radiopharmaceuticals / Q000032:analysis / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D011897:Random Allocation; D014018:Tissue Distribution
chemical_list: D005462:Fluorine Radioisotopes; D011724:Pyridazines; D019275:Radiopharmaceuticals; C428725:pyridaben
keywords: 18F labeling; MPI; biodistribution in mice; molecular imaging; pyridaben analog; radiopharmaceuticals