Quantification of neuroreceptors in the living human brain: III. D2-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 D2-like receptors in vivo in the neostriatum of normal living humans by using the graphical method. This method determines the D2-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 Dw 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 D2-like receptors that bind haloperidol in the caudate nucleus of normal humans declined 1% per year after the age of 18 years.
Wong
D F
DF
Department of Radiology and Radiological Sciences, Johns Hopkins Medical Institutions, Baltimore, MD 21287, USA.
Young
D
D
Wilson
P D
PD
Meltzer
C C
CC
Gjedde
A
A
D000375:Aging / Q000378:metabolism*; D000465:Algorithms; D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging; D001923:Brain Chemistry; D003198:Computer Simulation; D003342:Corpus Striatum / Q000737:chemistry / Q000000981:diagnostic imaging; D018491:Dopamine Agonists / Q000378:metabolism; D006168:Guinea Pigs; D006220:Haloperidol / Q000378:metabolism; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007700:Kinetics; D008297:Male; D008959:Models, Neurological; D009419:Nerve Tissue Proteins / Q000032:analysis* / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000032:analysis* / Q000378:metabolism; D012559:Schizophrenia / Q000000981:diagnostic imaging / Q000378:metabolism; D013134:Spiperone / Q000031:analogs & derivatives / Q000378:metabolism; D014055:Tomography, Emission-Computed
D018491:Dopamine Agonists; D009419:Nerve Tissue Proteins; D017448:Receptors, Dopamine D2; D013134:Spiperone; C039167:3-N-methylspiperone; D006220:Haloperidol