Age-dependent decline of dopamine D1 receptors in human brain: a PET study.

Radioligand binding studies in animals have demonstrated age-related loss of dopamine receptors in the caudate and putamen. In humans, while age-related declines in dopamine D2 receptors have been consistently reported, the effects of ageing on D1 receptors have been controversial. We used positron emission tomography (PET) with [11C]SCH 23390 to investigate dopamine D1 receptor binding in 21 normal volunteers aged 22-74 years. We also assessed their motor function with a Modified Columbia Score (MCS) and the Purdue Pegboard Test (PPBT). D1 binding potentials were derived using a graphical analysis with a cerebellar tissue input function. Standard linear regression techniques were used to determine the age-related rate of decline of D1 binding. We found an age-dependent decrease of D1 receptor binding in the caudate (6.9% per decade) and putamen (7.4% per decade). There was also a significant inverse correlation between [11C]SCH 23390 binding in the occipital cortex and age (8.6% decline per decade). PPBT score also decreased with age (P = 0.007). There was a direct correlation between PPBT score and D1 binding potential. We conclude that dopamine D1 receptor density declines with age and that the effects of physiological ageing may play a role in the expression of extrapyramidal disorders in the elderly.

Reproducibility of the distribution of carbon-11-SCH 23390, a dopamine D1 receptor tracer, in normal subjects.

UNLABELLED: The reproducibility of [11C]SCH 23390 in PET was studied in 10 normal human subjects. METHODS: The scan-to-scan variation of several measures used in PET data analysis, including the radioactivity ratio, plasma-input Logan total distribution volume (DV), plasma-input Logan DV ratio (DVR) and tissue-input Logan Bmax/Kd values, was determined. RESULTS: There were significant correlations among the radioactivity ratio, plasma-input DVR and tissue-input Bmax/Kd. With the cerebellum as the reference region, these three measures also had high reliability (86%-95%), high between-subject s.d. (7.7%-11.3%) and small within-subject s.d. (2.3%-3.6%), indicating that they are comparable and useful measures for the assessment of dopamine D1 receptor binding. CONCLUSION: The radioactivity ratio and the tissue-input Bmax/Kd may be preferred methods for the evaluation of dopamine D1 receptor binding because these two methods do not require arterial blood sampling and metabolite analysis. Our results show that cerebellum is a reliable reference region for SCH 23390. When the Logan plasma-input function method is used in data analysis for SCH 23390, DVRs rather than total DV values should be used because of the poor reliability of the DV values and their lack of correlation with other measures. Carbon-11-SCH 23390 is thus a reliable and reproducible ligand for the study of dopamine D1 receptor binding by PET.