1. ^*Department of Psychiatry, Columbia University College of Physicians and Surgeons, and Division of Brain Imaging, Department of Neuroscience, New York State Psychiatric Institute, New York, New York, U.S.A.
2. ^†Department of Radiology, Columbia University College of Physicians and Surgeons, and Division of Brain Imaging, Department of Neuroscience, New York State Psychiatric Institute, New York, New York, U.S.A.

Correspondence: Ramin V Parsey, New York State Psychiatric Institute, 1051 Riverside Dr, Unit 42, New York, NY, 10032, U.S.A.

Received 13 December 1999; Revised 12 April 2000; Accepted 13 April 2000.

Abstract

Serotonin 5-HT_1A receptors are implicated in the pathophysiology of neuropsychiatric conditions. The goal of this study was to evaluate methods to derive 5-HT_1A receptor parameters in the human brain with positron emission tomography (PET) and [carbonyl-¹¹C]WAY 100635. Five healthy volunteer subjects were studied twice. Three methods of analysis were used to derive the binding potential (BP), and the specific to nonspecific equilibrium partition coefficient (k₃/k₄). Two methods, kinetic analysis based on a three compartment model and graphical analysis, used the arterial plasma time-activity curves as the input function to derive BP and k₃/k₄. A third method, the simplified reference tissue model (SRTM), derived the input function from uptake data of a region of reference, the cerebellum, and provided only k₃/k₄. All methods provided estimates of regional 5-HT_1A receptor parameters that were highly correlated. Results were consistent with the known distribution of 5-HT_1A receptors in the human brain. Compared with kinetic BP, graphical analysis slightly under-estimated BP, and this phenomenon was mostly apparent in small size-high noise regions. Compared with kinetic k₃/k₄, the reference tissue method underestimated k₃/k₄ and the underestimation was apparent primarily in regions with high receptor density. Derivation of BP by both kinetic and graphical analysis was highly reliable, with an intraclass correlation coefficient (ICC) of 0.84 0.14 (mean SD of 15 regions) and 0.84 0.19, respectively. In contrast, the reliability of k₃/k₄ was lower, with ICC of 0.53 0.28, 0.47 0.28, and 0.55 0.29 for kinetic, graphical, and reference tissue methods, respectively. In conclusion, derivation of BP by kinetic analysis using the arterial plasma input function appeared as the method of choice because of its higher test-retest reproducibility, lower vulnerability to experimental noise, and absence of bias.