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Kinetic modeling of receptor-ligand binding applied to positron emission tomographic studies with neuroleptic tracers

Abstract

Positron emission tomography (PET) with labeled neuroleptics has made possible the study of neurotransmitter-receptor systems in vivo. In this study we investigate the kinetics of the 3,4-dihydroxyphenylethylamine (dopamine) receptor-ligand binding using PET data from a series of experiments in the baboon with the /sup 18/F-labeled drugs spiperone, haloperidol, and benperidol. Models used to describe these systems are based on first-order kinetics which applies at high specific activity (low receptor occupancy). The parameters governing the uptake and loss of drug from the brain were found by fitting PET data from regions with little or no receptor concentration (cerebellum) and from experiments in which specific binding was blocked by pretreatment with the drug (+)-butaclamol. Receptor constants were determined by fitting data from receptor-containing structures. Correcting the arterial plasma activities (the model driving function) for the presence of drug metabolites was found to be important in the modeling of these systems.
Publication Date:
Jan 01, 1987
Product Type:
Journal Article
Reference Number:
EDB-87-057920
Resource Relation:
Journal Name: J. Neurochem.; (United Kingdom); Journal Volume: 1
Subject:
59 BASIC BIOLOGICAL SCIENCES; 62 RADIOLOGY AND NUCLEAR MEDICINE; DOPAMINE; RECEPTORS; BIOCHEMICAL REACTION KINETICS; APES; BIOLOGICAL MODELS; CEREBELLUM; FLUORINE 18; LIGANDS; POSITRON COMPUTED TOMOGRAPHY; TRANQUILIZERS; AMINES; ANIMALS; AROMATICS; AUTONOMIC NERVOUS SYSTEM AGENTS; BETA DECAY RADIOISOTOPES; BETA-PLUS DECAY RADIOISOTOPES; BODY; BRAIN; CARDIOTONICS; CARDIOVASCULAR AGENTS; CENTRAL NERVOUS SYSTEM; CENTRAL NERVOUS SYSTEM AGENTS; COMPUTERIZED TOMOGRAPHY; DIAGNOSTIC TECHNIQUES; DRUGS; EMISSION COMPUTED TOMOGRAPHY; FLUORINE ISOTOPES; HOURS LIVING RADIOISOTOPES; HYDROXY COMPOUNDS; ISOTOPES; KINETICS; LIGHT NUCLEI; MAMMALS; MEMBRANE PROTEINS; NERVOUS SYSTEM; NEUROREGULATORS; NUCLEI; ODD-ODD NUCLEI; ORGANIC COMPOUNDS; ORGANS; PHENOLS; POLYPHENOLS; PRIMATES; PROTEINS; PSYCHOTROPIC DRUGS; RADIOISOTOPES; REACTION KINETICS; SYMPATHOMIMETICS; TOMOGRAPHY; VERTEBRATES; 550201* - Biochemistry- Tracer Techniques; 550601 - Medicine- Unsealed Radionuclides in Diagnostics
OSTI ID:
6764296
Research Organizations:
Brookhaven National Lab., Upton, NY
Country of Origin:
United Kingdom
Language:
English
Other Identifying Numbers:
Journal ID: CODEN: JONRA
Submitting Site:
NLM
Size:
Pages: 73-83
Announcement Date:

Citation Formats

Logan, J, Wolf, A P, Shiue, C Y, and Fowler, J S. Kinetic modeling of receptor-ligand binding applied to positron emission tomographic studies with neuroleptic tracers. United Kingdom: N. p., 1987. Web. doi:10.1111/j.1471-4159.1987.tb13129.x.
Logan, J, Wolf, A P, Shiue, C Y, & Fowler, J S. Kinetic modeling of receptor-ligand binding applied to positron emission tomographic studies with neuroleptic tracers. United Kingdom. doi:10.1111/j.1471-4159.1987.tb13129.x.
Logan, J, Wolf, A P, Shiue, C Y, and Fowler, J S. 1987. "Kinetic modeling of receptor-ligand binding applied to positron emission tomographic studies with neuroleptic tracers." United Kingdom. doi:10.1111/j.1471-4159.1987.tb13129.x. https://www.osti.gov/servlets/purl/10.1111/j.1471-4159.1987.tb13129.x.
@misc{etde_6764296,
title = {Kinetic modeling of receptor-ligand binding applied to positron emission tomographic studies with neuroleptic tracers}
author = {Logan, J, Wolf, A P, Shiue, C Y, and Fowler, J S}
abstractNote = {Positron emission tomography (PET) with labeled neuroleptics has made possible the study of neurotransmitter-receptor systems in vivo. In this study we investigate the kinetics of the 3,4-dihydroxyphenylethylamine (dopamine) receptor-ligand binding using PET data from a series of experiments in the baboon with the /sup 18/F-labeled drugs spiperone, haloperidol, and benperidol. Models used to describe these systems are based on first-order kinetics which applies at high specific activity (low receptor occupancy). The parameters governing the uptake and loss of drug from the brain were found by fitting PET data from regions with little or no receptor concentration (cerebellum) and from experiments in which specific binding was blocked by pretreatment with the drug (+)-butaclamol. Receptor constants were determined by fitting data from receptor-containing structures. Correcting the arterial plasma activities (the model driving function) for the presence of drug metabolites was found to be important in the modeling of these systems.}
doi = {10.1111/j.1471-4159.1987.tb13129.x}
journal = {J. Neurochem.; (United Kingdom)}
volume = {1}
journal type = {AC}
place = {United Kingdom}
year = {1987}
month = {Jan}
}