Quantification of neuroreceptors in the living human brain .3. D-2-like dopamine receptors: Theory, validation, and changes during normal aging

Dopamine receptor density is believed to decline in normal aging. To test this hypothesis, we measured the density of dopamine D-2-like receptors in vivo in the neostriatum of normal living humans by using the graphical method. This method determines the D-2-like dopamine receptor density in the human brain with an occupying ligand (unlabeled haloperidol) and a radioligand (labeled 3-N-methylspiperone). The method was examined critically, and the assumptions underlying the method were shown to be valid. The validation included comparison of the representation of tracer metabolism by high-pressure liquid chromatography and model assays, calculation of the lumped constant D-w from the value of its components, and comparable tracer partition coefficients in vitro and in vivo. In error analysis, the method consistently performed as well as the direct least-squares regression at statistical noise levels appropriate for the tomograph used in these studies. The method revealed that the density of the D-2-like receptors that bind haloperidol in the caudate nucleus of normal humans declined 1% per year after the age of 18 years.