TY - JOUR
T1 - Quantification of neuroreceptors in the living human brain
T2 - III. D2- like dopamine receptors: Theory, validation, and changes during normal aging
AU - Wong, Dean F.
AU - Young, David
AU - Wilson, P. David
AU - Meltzer, Carolyn Cidis
AU - Gjedde, Albert
PY - 1997/3
Y1 - 1997/3
N2 - Dopamine receptor density is believed to decline in normal aging. To test this hypothesis, we measured the density of dopamine D2-1ike 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 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 D2-like receptors that bind haloperidol in the caudate nucleus of normal humans declined 1% per year after the age of 18 years.
AB - Dopamine receptor density is believed to decline in normal aging. To test this hypothesis, we measured the density of dopamine D2-1ike 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 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 D2-like receptors that bind haloperidol in the caudate nucleus of normal humans declined 1% per year after the age of 18 years.
KW - Dopamine receptors
KW - Positron emission tomography
KW - Receptor quantification
KW - Schizophrenia
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U2 - 10.1097/00004647-199703000-00009
DO - 10.1097/00004647-199703000-00009
M3 - Article
C2 - 9119905
AN - SCOPUS:0030889597
SN - 0271-678X
VL - 17
SP - 316
EP - 330
JO - Journal of Cerebral Blood Flow and Metabolism
JF - Journal of Cerebral Blood Flow and Metabolism
IS - 3
ER -