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Translational possibility of [18F]Mefway to image serotonin 1A receptors in humans: Comparison with [18F]FCWAY in rodents

 Jae Yong Choi  ;  Byoung Soo Kim  ;  Chul Hoon Kim  ;  Dong Goo Kim  ;  Sang Jin Han  ;  Kyochul Lee  ;  Kyeong Min Kim  ;  Gwangil An  ;  Tae Hyun Choi  ;  Sun Dong Yoo  ;  Young Hoon Ryu 
 SYNAPSE, Vol.68(12) : 595-603, 2014 
Journal Title
Issue Date
serotonin 1A receptors ; [18F]Mefway ; [18F]FCWAY ; microPET
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-HT1A ) 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-HT1A target regions) and the cerebellum (5-HT1A 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 (BPND ) as a steady-state binding parameter. Finally, binding affinities to 5-HT1A receptors were assessed in Chinese hamster ovary cells (CHO-K1) cells expressing human recombinant 5-HT1A 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 BPND (at hippocampus, peak brain uptakes: 6.9 vs. 8.5, target-to-nontarget ratios: 6.9 vs. 8.5, BPND : 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 (IC50 : 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.
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1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Nuclear Medicine (핵의학교실) > 1. Journal Papers
Yonsei Authors
Kim, Chul Hoon(김철훈) ORCID logo https://orcid.org/0000-0002-7360-429X
Ryu, Young Hoon(유영훈) ORCID logo https://orcid.org/0000-0002-9000-5563
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