||Brain PET study using [11C]BU99008 in Zucker fatty versus lean rats.
Kawamura, Kazunori ,
Yamasaki, Tomoteru ,
Zhang, Yiding ,
Wakizaka, Hidekatsu ,
Hatori, Akiko ,
Xie, Lin ,
Fujinaga, MasayukiMing-Rong, Zhang
Objectives: [11C]BU99008 was developed as a positron emission tomography (PET) probe for imaging of I2-imidazoline receptor (I2R) . [11C]BU99008 displayed a selective and high affinity for I2R (Ki, 1.4 nmol/L ), and relatively high brain penetration and specific binding by brain PET studies in the rat , porcine  and monkey . The I2Rs have been linked to several central nervous system disorders, and I2R proteins have not been encoded and their functional role remains uncertain. Additionally, I2Rs have been found in the hypothalamus and it has reported that selective I2R ligands promoted food intake, which is presumed to be an effect of eating function through the hypothalamus known as a feeding center [5,6]. Here, we performed brain PET study using [11C]BU99008 in Zucker fatty and lean rats as a useful in vivo imaging agent for eating function.Methods: [11C]BU99008 was prepared by methylation of the BU-precursor and [11C]methyl iodide. Dynamic PET scans were acquired in Zucker fatty and lean rats, radioactivity and metabolites of plasma were measured, and the kinetic parameters were estimated based on these results.Results: [11C]BU99008 was synthesized with a suitable radioactivity for the injection. In the PET study, the radioactivity levels after the injection of [11C]BU99008 in the hypothalamus of both Zucker fatty and lean 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 Zucker fatty rats was about 1.3 times higher than that of Zucker lean rats. The distribution volume (VT) estimated by Logan graphical analysis in the hypothalamus of Zucker fatty rats was about 1.8 times higher than that in Zucker lean rats. In metabolite analysis, unchanged radiolabeled form showed the tendency to a gradual decrease for 60 min after the injection in both Zucker fatty and lean rats.Conclusion: In the PET study using [11C]BU99008, we demonstrated that the accumulated radioactivity and estimated VT value in the feeding center of Zucker fatty rats were higher than that of Zucker lean rats. PET study using [11C]BU99008 would contribute to in vivo imaging of the eating function.References:  Kealey S, et al. J Nucl Med. 2013;54:139-44.  Tyacke RJ, et al. Synapse. 2012;66:542-51.  Kawamura K, et al. Nucl Med Biol. 2017;45:1-7.  Parker CA, et al. J Nucl Med. 2014;55:838-44.  Nutt DJ, et al. Ann NY Acad Sci. 1995;763:125-39.  Polidori et al. Eur J Pharmacol. 2000;392:41-9.
2017 World Molecular Imaging Congress(WMIC2017)にポスター発表の為。