期刊
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
卷 25, 期 7, 页码 785-793出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1038/sj.jcbfm.9600072
关键词
brain; [C-11]WAY-100635; modeling; PET; reference tissue; serotonin
资金
- NIMH NIH HHS [MH62185, MH40695, MH01603, MH40210] Funding Source: Medline
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-HT1A ligand [C-11]WAY-100635 is sensitive to changes in the free and nonspecific binding of the ligand in the reference region (V,). Healthy female volunteers have higher 5-HT1A 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-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 V-3. A quantitative autoradiogram in human brain using [H-3]WAY-100635 identified a cerebellar subregion devoid of 5-HT1A receptors. In vivo 5-HT1A receptors were evaluated using [C-11]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 (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-HT1A studies using [C-11]WAY-100635. With CW as a reference region, V-3 cannot be used to detect differences in 5-HT1A receptors between men and women, suggesting the need for arterial input functions to determine BP.
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