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07.05.2018 | Research Article

Change in the Binding of [¹¹C]BU99008 to Imidazoline I₂ Receptor Using Brain PET in Zucker Rats

verfasst von: Kazunori Kawamura, Tomoteru Yamasaki, Yiding Zhang, Hidekatsu Wakizaka, Akiko Hatori, Lin Xie, Masayuki Fujinaga, Ming-Rong Zhang

Erschienen in: Molecular Imaging and Biology | Ausgabe 1/2019

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Abstract

Purpose

The imdazoline I₂ receptor (I₂R) has been found in the feeding centers of the brain, such as the hypothalamus, and certain I₂R ligands have been reported to stimulate food intake. Thus, it has been proposed that I₂R may play a role in feeding control. [¹¹C]BU99008 was developed as a positron emission tomography (PET) tracer for imaging of I₂R. [¹¹C]BU99008 displayed relatively high brain penetration and specific binding by brain PET studies in preclinical studies. Here, we evaluated a pathological condition caused by obesity related to I₂R function by quantitative PET study using [¹¹C]BU99008.

Procedures

PET scans were acquired in the Zucker (ZUC) lean and fatty rats, radioactivity and metabolites of plasma were measured, and the kinetic parameters were estimated.

Results

Radioactivity levels after the injection of [¹¹C]BU99008 in the hypothalamus of both ZUC lean and fatty rats were highly accumulated, and then gradually decreased until 60 min after the injection. The accumulated radioactivity from 30 to 60 min after the injection in the hypothalamus of the ZUC fatty rats was 1.3 times greater than that of lean rats. The volume of distribution (V_T) estimated by Logan graphical analysis in the hypothalamus of the ZUC fatty rats was 1.8 times greater than that in the ZUC lean rats. In metabolite analysis, the percentages of the unchanged form in the plasma of the ZUC fatty rats at 60 min after the injection (5.0 %) was significantly lower than that of lean rats (9.1 %).

Conclusions

By PET imaging using [¹¹C]BU99008, we demonstrated that the accumulated radioactivity and estimated V_T value in the feeding center of ZUC lean rats was lower than that in fatty rats. PET studies using [¹¹C]BU99008 may contribute to elucidate a pathological condition caused by obesity related to I₂R function.

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Titel: Change in the Binding of [11C]BU99008 to Imidazoline I2 Receptor Using Brain PET in Zucker Rats
verfasst von: Kazunori Kawamura
Tomoteru Yamasaki
Yiding Zhang
Hidekatsu Wakizaka
Akiko Hatori
Lin Xie
Masayuki Fujinaga
Ming-Rong Zhang
Publikationsdatum: 07.05.2018
Verlag: Springer International Publishing
Erschienen in: Molecular Imaging and Biology / Ausgabe 1/2019
Print ISSN: 1536-1632
Elektronische ISSN: 1860-2002
DOI: https://doi.org/10.1007/s11307-018-1206-y

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Change in the Binding of [¹¹C]BU99008 to Imidazoline I₂ Receptor Using Brain PET in Zucker Rats