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Brain PET imaging using [11C]Cimbi-36 in Zucker fatty versus lean rats
https://repo.qst.go.jp/records/76737
https://repo.qst.go.jp/records/767379a59e65b-9267-49fb-9ee3-db0e98eb820c
| Item type | 会議発表用資料 / Presentation(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2019-09-05 | |||||
| タイトル | ||||||
| タイトル | Brain PET imaging using [11C]Cimbi-36 in Zucker fatty versus lean rats | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_c94f | |||||
| 資源タイプ | conference object | |||||
| アクセス権 | ||||||
| アクセス権 | metadata only access | |||||
| アクセス権URI | http://purl.org/coar/access_right/c_14cb | |||||
| 著者 |
Kawamura, Kazunori
× Kawamura, Kazunori× Yamasaki, Tomoteru× Wakizaka, Hidekatsu× Hatori, Akiko× Zhang, Yiding× Xie, Lin× Ming-Rong, Zhang× Kawamura, Kazunori× Yamasaki, Tomoteru× Wakizaka, Hidekatsu× Hatori, Akiko× Zhang, Yiding× Xie, Lin× Ming-Rong, Zhang |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Objectives: Central serotonin (5-HT) has suppressive effects on food intake and body weight. Serotonin 2A (5-HT2A) receptor gene expression was increased in association with obesity, and pharmacologic inactivation of 5-HT2A receptors suppressed hyperphagia and body weight gain [1]. Thus, 5-HT2A receptors have a role in the regulation of feeding and energy homeostasis. Also, pharmacological studies supported a specific role for 5-HT2C receptor in the regulation of energy balance and body weight [2]. Recently, a selective 5-HT2C receptor agonist (Belviq, lorcaserin hydrochloride) was officially approved for use in the treatment of obesity [3]. [11C]Cimbi-36 is a 5-HT2A and 5-HT2C receptors agonist PET tracer that has been applied for human PET study [4]. Furthermore, [11C]Cimbi-36 binding is sensitive for changes in endogenous 5-HT levels, although PET is only detectable when the 5-HT release is sufficiently high [5]. Here, we evaluated changes of 5-HT2A and 5-HT2C receptors density or 5-HT levels in obese by the PET study using [11C]Cimbi-36 in Zucker (ZUC) fatty and lean rats. Methods: [11C]Cimbi-36 was prepared as described previously [6]. Dynamic PET scans were acquired in ZUC fatty (Leprfa/Leprfa; 8-9 weeks old [w.o.]; 400 ± 21 g body weight [b.w.], n = 5) and lean rats (Leprfa/+ or +/+; 8-9 w.o.; 275 ± 17 g b.w.; n = 5), and the kinetic parameters were estimated based on these results by the simplified reference tissue model (SRTM). In vitro autoradiography study was also performed in the brain section of ZUC fatty and lean rats. Results: In the PET study, the radioactivity levels after the injection of [11C]Cimbi-36 in the frontal cortex of both ZUC fatty and lean rats accumulated highly, and then gradually decreased until 60 min after the injection. The accumulated radioactivity from 30 to 60 min after the injection in the frontal cortex of ZUC fatty rats was slightly higher than that of ZUC lean rats. The binding potential (BPND) estimated by the SRTM in the frontal cortex of ZUC fatty rats was significantly higher than that in ZUC lean rats (about 1.2 times), although the radioactivity levels in the frontal cortex of ZUC fatty and lean rats were almost same in in vitro autoradiography study. These results suggest that the concentration of 5-HT in fatty rats may be lower than that in lean rats based on multiple effects of 5-HT density. Thus, it is considered that the binding of [11C]Cimbi-36 in fatty rats was increased, because the blocking effect by relatively low concentrations of 5-HT on the binding in the fatty rats was smaller than the corresponding blocking effect in the lean rats. Conclusion: Using PET study with [11C]Cimbi-36, we demonstrated that the accumulated radioactivity and estimated BPND value in the frontal cortex in ZUC fatty rats were higher than those in lean rats. PET studies using [11C]Cimbi-36 may be helpful for estimating multiple changes of 5-HT in the brain. References: [1] Nonogaki K, et al. Biochem Biophys Res Commun. 2006;351:1078-82.; [2] Burke LK, et al. J Neuroendcrinol 2015;27:389-98.; [3] Oh CM, et al. Diabetes Metab J. 2016;40:89-98.; [4] Ettrup A, et al. J Cereb Blood Flow Metab. 2014;34:1188-96.; [5] Jørgensen LM, et al J Cereb Blood Flow Metab. 2017;37:425-34.; [6] Ettrup A, et al. Eur J Nucl Med Mol Imaging 2011 38 681-93. |
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| 会議概要（会議名, 開催地, 会期, 主催者等） | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | WMIC2019でのポスター発表 | |||||
| 発表年月日 | ||||||
| 日付 | 2019-09-06 | |||||
| 日付タイプ | Issued | |||||
