Dissociative changes in the bmax and K_D of dopamine D2/D3 receptors with aging observed in functional subdivisions of the striatum: A revisit with an improved data analysis method

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 D2/D3 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. Methods: In response, a new method (bolus-plusinfusion transformation [BPIT]) was developed. After completion of a validation study for ¹¹C-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. Results: 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 ageassociated declines in B_max in all 5 functional striatal subdivisions with BPIT when corrected for multiple comparisons. These agerelated effects were not consistently attainable with the transient equilibrium method. Irrespective to methods, K_D remained unchanged with age. Conclusion: 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.