Further development and validation of the model for in vivo quantification of human dopamine receptors

Conference · Wed May 01 04:00:00 EDT 1985 · J. Nucl. Med.; (United States)

OSTI ID:6855886

Wong, D F; Gjedde, A; Wagner, Jr, H N; Douglass, K H; Dannels, R F; Snyder, S H; Kuhar, M J

A goal in neuroreceptor PET imaging is to estimate receptor density (Bmax) and affinity (KD). Previously the authors reported the linearity of the Caudate/Cerebellar activity (CA/CB) with time in 100 subjects injected with C-11 n-methylspiperone (NMSP). In the proposed 3 compartment model the binding rate to the receptor, K3 was the slope of CA/CB vs. 'exposure time', i.e. the plasma conc. integral/plasma conc. of NMSP (PI/P). The authors have now expanded the model to estimate B/sub max/ and K/sub D/. They have observed in 10 normal subjects: The CB distribution vol. (CB/plasma activity) decreased with PI/P indicating some plasma metabolites did not cross into brain. The CA dist. volume increased with PI/P becoming linear because of specific binding of the ligand to the receptor with negligible dissociation. The CB vs. PI/P curve was used to calculate a metabolite corrected plasma curve which correlated well with HPLC measurements. The corrected plasma curve was then used to estimate a new PI/P (NPI/P). The K3 estimated from the slope of CA/CB vs. NPI/P (ranged .015-.024/min.) After blocking the receptors with unlabelled haloperidol (H) (N=2), an estimate of the inhibitory constant Ki for H (1.7, 2.0 nM) and (Bmax)*(koff) was obtained. The koff dissociation rate for H) was assumed to be the -.13/min., yielding a Bmax (30, 35 pM) which is comparable to in vitro human data. Thus, using 2 different mass injection of labelled C-11 NMSP or 1 with and without a cold competing ligand, in vivo dopamine receptor affinity and Bmax can be estimated. The model can be extended to serotonin receptors where the authors found a significant dissociation (k4).

• Research Organization: The Johns Hopkins Medical Institutions, Baltimore, MD
• OSTI ID: 6855886
• Report Number(s): CONF-850611-
• Conference Information: Journal Name: J. Nucl. Med.; (United States) Journal Volume: 26:5
• Country of Publication: United States
• Language: English

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59 BASIC BIOLOGICAL SCIENCES
62 RADIOLOGY AND NUCLEAR MEDICINE
AMINES
AROMATICS
AUTONOMIC NERVOUS SYSTEM AGENTS
BETA DECAY RADIOISOTOPES
BETA-PLUS DECAY RADIOISOTOPES
BIOCHEMICAL REACTION KINETICS
BIOCHEMISTRY
BLOOD CHEMISTRY
BODY
BRAIN
CARBON 11
CARBON ISOTOPES
CARDIOTONICS
CARDIOVASCULAR AGENTS
CENTRAL NERVOUS SYSTEM
CEREBELLUM
CEREBRUM
CHEMICAL PREPARATION
CHEMISTRY
COMPUTERIZED TOMOGRAPHY
CORRELATIONS
COUNTING TECHNIQUES
DATA ANALYSIS
DIAGNOSTIC TECHNIQUES
DISTRIBUTION
DOPAMINE
DOSE-RESPONSE RELATIONSHIPS
DRUGS
EMISSION COMPUTED TOMOGRAPHY
EVEN-ODD NUCLEI
HYDROXY COMPOUNDS
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
LABELLED COMPOUNDS
LABELLING
LIGANDS
LIGHT NUCLEI
MATHEMATICAL MODELS
MEMBRANE PROTEINS
METABOLISM
MINUTES LIVING RADIOISOTOPES
NERVOUS SYSTEM
NEUROREGULATORS
NUCLEI
ORGANIC COMPOUNDS
ORGANS
PHENOLS
POLYPHENOLS
POSITRON COMPUTED TOMOGRAPHY
PROTEINS
RADIOISOTOPE SCANNING
RADIOISOTOPES
RADIOPHARMACEUTICALS
RADIORECEPTOR ASSAY
REACTION KINETICS
RECEPTORS
SCINTISCANNING
SYMPATHOMIMETICS
SYNTHESIS
TISSUE DISTRIBUTION
TOMOGRAPHY
TRACER TECHNIQUES