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Two measures used in brain imaging are binding potential (BP) and the specific to nonspecific equilibrium partition coefficient ( V 3 “). V 3 ” determined using the 5-HT 1A  ligand [ 11 C]WAY-100635 is sensitive to changes in the free and nonspecific binding of the ligand in the reference region ( V 2 ). Healthy female volunteers have higher 5-HT 1A  BP but not V 3 “ compared with men, because V 2  is higher in women. While there could be several explanations for this observation, we hypothesized that women have more 5-HT 1A  receptors in the cerebellum. We explore the cerebellum to define a subregion that more accurately represents the free and nonspecific binding, potentially allowing the use of V 3 ”. A quantitative autoradiogram in human brain using [ 3 H]WAY-100635 identified a cerebellar subregion devoid of 5-HT 1A  receptors. In vivo 5-HT 1A  receptors were evaluated using [ 11 C]WAY-100635 in 12 healthy women and 13 healthy men. Each subject had a metabolite-corrected arterial input function. The autoradiogram demonstrates the lowest concentration of 5-HT 1A  receptors in the cerebellar white matter (CW) and highest concentration in the cerebellar vermis (CV). The CW volume of distribution ( V T ) is lower than CV. Cerebellar white matter is adequately modeled by a one-tissue compartmental model, while a two-tissue model is necessary to model CV or the total cerebellum (CT). Women have a higher CW V T  compared with men, suggesting a difference in V 2 . Use of CW improves identifiability and time stability of BP in cortical regions. Cerebellar white matter might be a better reference region for use in future 5-HT 1A  studies using [ 11 C]WAY-100635. With CW as a reference region, V 3 “ cannot be used to detect differences in 5-HT 1A  receptors between men and women, suggesting the need for arterial input functions to determine BP.

Regional Heterogeneity of 5-HT1A Receptors in Human Cerebellum as Assessed by Positron Emission Tomography

Regional Heterogeneity of 5-HT_1A Receptors in Human Cerebellum as Assessed by Positron Emission Tomography