1. ¹The Vivian Rakoff Positron Emission Tomography Unit, Centre for Addiction and Mental Health, Toronto, Ontario, Canada
2. ²Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada
3. ³Département Universitaire de Psychiatrie, Unité de Neuroimagerie, Université de Genève, Geneva, Switzerland

Correspondence: Dr N Ginovart, PET Centre, CAMH, 250 College Street, Toronto, Ontario, Canada M5T 1R8. E-mail: nathalie.ginovart@medecine.unige.ch

Received 20 June 2006; Revised 31 August 2006; Accepted 5 September 2006; Published online 11 October 2006.

Abstract

The kinetic modeling of [¹¹C]-(+)-PHNO binding to the dopamine D_2/3 receptors in six human volunteers using positron emission tomography (PET) is described. [¹¹C]-(+)-PHNO is the first agonist radioligand for the D_2/3 in humans and as expected showed high uptake in caudate, putamen, globus pallidus (GP) and ventral striatum, and low uptake in cerebellum. A two-tissue compartment model (2CM) with four parameters was necessary to adequately fit time–activity data in all regions. Although a 2CM provided an excellent estimation of total distribution volumes, which were highly correlated with those obtained with the invasive Logan approach, it provided a poor identification of the k₃/k₄ ratios. Coupling K₁/k₂ between brain regions (Method C) or fixing K₁/k₂ to the value obtained in cerebellum (Method D) enabled more stable estimates of k₃/k₄ as compared with an unconstrained 2CM. The k₃/k₄ obtained with Method D ranged from 0.120.03 in cerebellum to 3.930.77 in GP and were similar to those obtained when coupling K₁/k₂. Binding potentials (BPs) obtained using the simplified reference tissue model (BP_SRTM) ranged from 2.080.34 in caudate to 3.550.78 in GP and were highly correlated with k₃/k₄ estimates obtained with Method D (r=0.98). However, BP_SRTM were 11%5% lower than values obtained with Method D. BPs derived using the noninvasive Logan approach were slightly lower but not significantly different than BP_SRTM. This study demonstrates that [¹¹C]-(+)-PHNO can be used for the quantitative measurement of D_2/3 densities and should enable further studies of potential D_2/3 dysregulation in several important psychiatric and neurologic illnesses.