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

PurposeThe imdazoline I-2 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. [C-11]BU99008 was developed as a positron emission tomography (PET) tracer for imaging of I2R. [C-11]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 [C-11]BU99008.ProceduresPET scans were acquired in the Zucker (ZUC) lean and fatty rats, radioactivity and metabolites of plasma were measured, and the kinetic parameters were estimated.ResultsRadioactivity levels after the injection of [C-11]BU99008 in the hypothalamus of both ZUC lean and fatty rats were highly accumulated, and then gradually decreased until 60min after the injection. The accumulated radioactivity from 30 to 60min 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 60min after the injection (5.0%) was significantly lower than that of lean rats (9.1%).ConclusionsBy PET imaging using [C-11]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 [C-11]BU99008 may contribute to elucidate a pathological condition caused by obesity related to I2R function.