1. ¹Department of Neuroscience, New York State Psychiatric Institute, New York, New York, USA
2. ²Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, New York, USA
3. ³Department of Radiology, Columbia University College of Physicians and Surgeons, New York, New York, USA

Correspondence: Dr Ramin Parsey, Department of Neuroscience, New York State Psychiatric Institute, 1051 Riverside Drive, Box #42, New York, NY 10032, USA. E-mail: rparsey@neuron.cpmc.columbia.edu

Received 7 June 2004; Revised 14 September 2004; Accepted 1 December 2004; Published online 16 February 2005.

Abstract

Two measures used in brain imaging are binding potential (BP) and the specific to nonspecific equilibrium partition coefficient (V₃"). V₃" determined using the 5-HT_1A ligand [¹¹C]WAY-100635 is sensitive to changes in the free and nonspecific binding of the ligand in the reference region (V₂). Healthy female volunteers have higher 5-HT_1A BP but not V₃" compared with men, because V₂ 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 V₃". A quantitative autoradiogram in human brain using [³H]WAY-100635 identified a cerebellar subregion devoid of 5-HT_1A receptors. In vivo 5-HT_1A receptors were evaluated using [¹¹C]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 V₂. 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 [¹¹C]WAY-100635. With CW as a reference region, V₃" 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.