LONG-TERM STABILITY OF NEUROTRANSMITTER ACTIVITY INVESTIGATED WITH C-11 RACLOPRIDE PET

There is evidence for the shift of regulatory setpoints of functionall y linked neurotransmitter systems as a basis of psychiatric disorders. C-11-raclopride PET, which has been shown to be sensitive to changes in endogenous dopamine and has a high short-term test-retest reliabili ty, can be used to investigate different regulatory states of the dopa minergic system with respect to psychiatric diseases and pharmacologic al influences. Prior to these studies, the reliability of the method o ver time has to be established. The current study was performed in ord er to evaluate the long-term stability of the striatal dopaminergic sy stem. Eight normal healthy subjects (mean age: 48.1 years; range: 24-7 5) were studied twice with C-11-raclopride PET two times under resting conditions with a mean time interval between the scans of 11.3 months (range: 1-19). The ratio of basal ganglia (BG) to cerebellar (CB) dis tribution volumes (DVs) revealed a mean absolute change of 6.94 (range : 0.0-12.87%) between study A and B. BG DVs mean absolute change was 6 .30% (range: 0.55-30.46%), CB DVs mean absolute change was 8.65% (rang e: 3.51-16.33%). The mean change of the BG/CB ratio was -0.33% (range: 12.87-12.34%). BG DVs mean change was 4.55% (range: 4.2-30.46%), CB D Vs mean change was 5.10% (range: -10.71-16.33%). The intraindividual d ifferences between the two scans in our study were not significantly d ifferent as compared to the 24 hour interval test-retest data, which h ave been published earlier (repeated measures ANOVA with df = 11; F = 0.49; P = 0.50) [Volkow et al. (1993) J. Nucl. Med., 34:609-613]. The intraclass correlation of the DV ratio index was r = 0.81. The binding potential in the baseline scans and repeated scans showed a non-signi ficant correlation with age (r = -0.58, P = 0.13). Interindividually, the DV ratio index revealed a mean of 3.18 (range = 2.55-3.68, SD = 0. 42 in study A and of 3.16 (range 2.37-3.57, SD = 0.41) in study B. The intrasubject stability of the C-11-raclopride binding over a long-ter m period in normal human subjects suggests the feasibility of study de signs investigating the long-term changes of the dopaminergic responsi vity after pharmacological challenges. The baseline stability will als o serve as a necessary reference for further dose-response studies and investigations of subchronical pharmacological interventions. (C) 199 8 Wiley-Liss, Inc.