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Translational possibility of [ 18 F]Mefway to image serotonin 1A receptors in humans: Comparison with [ 18 F]FCWAY in rodents
Author(s) -
Choi Jae Yong,
Kim Byoung Soo,
Kim Chul Hoon,
Kim Dong Goo,
Han Sang Jin,
Lee Kyochul,
Kim Kyeong Min,
An Gwangil,
Choi Tae Hyun,
Yoo Sun Dong,
Ryu Young Hoon
Publication year - 2014
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/syn.21771
Subject(s) - microsome , receptor , chinese hamster ovary cell , serotonin , hippocampus , human brain , in vivo , chemistry , cerebellum , in vitro , medicine , endocrinology , biochemistry , biology , neuroscience , microbiology and biotechnology
Purpose: To compare the cerebral uptake and binding potential of [ 18 F]FCWAY and [ 18 F]Mefway in the rodent to assess their potential for imaging serotonin 1A (5‐HT 1A ) receptors. Materials and Methods: In vitro liver microsomal studies were performed to evaluate the degree of defluorination. Dynamic positron emission tomography (PET) studies were then conducted for 2 h with or without an anti‐defluorination agent. The regions of interest were the hippocampus and frontal cortex (5‐HT 1A target regions) and the cerebellum (5‐HT 1A nontarget region). The in vivo kinetics of the radioligands were compared based on the brain uptake values and target‐to‐nontarget ratio. We also performed a comparison of binding potential (BP ND ) as a steady‐state binding parameter. Finally, binding affinities to 5‐HT 1A receptors were assessed in Chinese hamster ovary cells (CHO‐K1) cells expressing human recombinant 5‐HT 1A receptors. Results: The radiochemical yield of [ 18 F]Mefway was slightly higher than that of [ 18 F]FCWAY (19 vs. 15%). With regard to metabolic stability against defluorination, both compounds exhibited similar stability in rat liver microsomes, but [ 18 F]Mefway displayed higher stability in the human microsome (defluorination ratio at 30 min: 32 vs. 29 in rat liver microsomes, 31 vs. 64 in human liver microsomes for [ 18 F]Mefway and [ 18 F]FCWAY, respectively). There were no significant differences in brain uptake, the target‐to‐nontarget ratios, and the BP ND (at hippocampus, peak brain uptakes: 6.9 vs. 8.5, target‐to‐nontarget ratios: 6.9 vs. 8.5, BP ND : 5.2 vs. 6.2 for [ 18 F]Mefway and [ 18 F]FCWAY). The binding affinity of [ 18 F]Mefway was considerably higher than that of [ 18 F]FCWAY (IC 50 : 1.5 nM vs. 2.2 nM). Conclusion: [ 18 F]Mefway exhibits favorable characteristics compared to [ 18 F]FCWAY in rodents, and may be a promising radioligand for use in human subjects. Synapse 68:595–603, 2014 . © 2014 Wiley Periodicals, Inc.