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

• Published in: Journal of cerebral blood flow and metabolism Vol. 25; no. 7; pp. 785 - 793
• Main Authors: Parsey, Ramin V, Arango, Victoria, Olvet, Doreen M, Oquendo, Maria A, Van Heertum, Ronald L, Mann, J John
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 01.07.2005; Lippincott Williams & Wilkins; Sage Publications Ltd
• Subjects: Adult; Autoradiography; Biological and medical sciences; Cerebellum - cytology; Cerebellum - diagnostic imaging; Cerebellum - metabolism; Female; Fundamental and applied biological sciences. Psychology; Humans; Investigative techniques, diagnostic techniques (general aspects); Kinetics; Magnetic Resonance Imaging; Male; Medical sciences; Motor control and motor pathways. Reflexes. Control centers of vegetative functions. Vestibular system and equilibration; Nervous system; Neurology; Piperazines - metabolism; Positron-Emission Tomography; Pyridines - metabolism; Radionuclide investigations; Receptor, Serotonin, 5-HT1A - metabolism; Sex Characteristics; Vascular diseases and vascular malformations of the nervous system; Vertebrates: nervous system and sense organs; brain[11C]WAY-100635; serotonin; modeling; reference tissue; PET; Cerebellum; Radionuclide study; Human; Nervous system diseases; Serotonin; brain; Modeling; Cerebral disorder; Heterogeneity; [11C]WAY-100635; Central nervous system disease; Neurotransmitter; Positron emission tomography; Cerebrovascular disease; Positron; Emission tomography
• ISSN: 0271-678X; 1559-7016
• DOI: 10.1038/sj.jcbfm.9600072

Two measures used in brain imaging are binding potential (BP) and the specific to nonspecific equilibrium partition coefficient (V3“). V3” determined using the 5-HT1A 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-HT1A 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-HT1A 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-HT1A receptors. In vivo 5-HT1A 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-HT1A receptors in the cerebellar white matter (CW) and highest concentration in the cerebellar vermis (CV). The CW volume of distribution (VT) 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 VT 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-HT1A studies using [11C]WAY-100635. With CW as a reference region, V3“ cannot be used to detect differences in 5-HT1A receptors between men and women, suggesting the need for arterial input functions to determine BP.