Dissociative changes in the Bmax and KD of dopamine D2/D3 receptors with aging observed in functional subdivisions of the striatum: a revisit with an improved data analysis method.

Abstract

Separate measurements of B(max), the density of available receptors, and K(D), the equilibrium dissociation constant in the human brain, with PET have contributed to our understanding of neuropsychiatric disorders, especially with respect to the dopamine D(2)/D(3) receptor system. However, existing methods have limited applications to the whole striatum, putamen, or caudate nucleus. Improved methods are required to examine B(max) and K(D) in detailed functional striatal subdivisions that are becoming widely used. In response, a new method (bolus-plus-infusion transformation [BPIT]) was developed. After completion of a validation study for (11)C-raclopride scans involving 81 subjects, age-associated changes in B(max) and K(D) were examined in 47 healthy subjects ranging in age from 18 to 77 y. The BPIT method was consistent with established reference tissue methods regarding regional binding potential. BPIT yielded time-consistent estimates of B(max) and K(D) when scan and infusion lengths were set equal in the analysis. In addition, BPIT was shown to be robust against PET measurement errors when compared with a widely accepted transient equilibrium method. Altogether, BPIT was supported as a method for regional binding potential, B(max), and K(D). We demonstrated age-associated declines in B(max) in all 5 functional striatal subdivisions with BPIT when corrected for multiple comparisons. These age-related effects were not consistently attainable with the transient equilibrium method. Irrespective to methods, K(D) remained unchanged with age. The BPIT approach may be useful for understanding dopamine receptor abnormalities in neuropsychiatric disorders by enabling separate measurements of B(max) and K(D) in functional striatal subdivisions.