Models for in vivo kinetic interactions of dopamine D2-neuroreceptors and 3-(2'-( sup 18 F)fluoroethyl)spiperone examined with positron emission tomography

Journal Article · Thu Nov 30 23:00:00 EST 1989 · Journal of Cerebral Blood Flow and Metabolism; (USA)

DOI:https://doi.org/10.1038/jcbfm.1989.118· OSTI ID:7068370

Bahn, M M; Huang, S C; Hawkins, R A; Satyamurthy, N; Hoffman, J M; Barrio, J R; Mazziotta, J C; Phelps, M E ^[1]

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1. Univ. of California, Los Angeles (USA)

The in vivo tracer kinetics of 3-(2'-(18F)fluoroethyl)spiperone (FESP) in the caudate/striatum and cerebellar regions of the human and monkey brain were studied with positron emission tomography (PET). The minimal model configuration that can describe the kinetics was determined statistically. Three two-compartment model configurations were found to be suitable for describing the kinetics in caudate/striatum and cerebellum: (1) a nonlinear model (five parameters) applicable to studies using nontracer (partially saturating) quantities of FESP in monkey striatum, (2) a linear four-parameter model applicable to the caudate/striatal and cerebellar kinetics in human and monkey studies with tracer quantities of FESP, and (3) a linear three-parameter model derived from the four-parameter model by assuming irreversible binding applicable to tracer studies of the human caudate. In the human studies, when the caudate kinetics (n = 4) were fit by model 2 (with four parameters), the value of the in vivo ligand dissociation constant kd was found to be 0.0015 +/- 0.0032/min. The three-parameter model (model 3) was found to fit the data equally well: this model is equivalent to model 2 with kd set to zero. In the monkey studies, it was found that for short (90 min) studies using tracer quantities of FESP, model 2 fit the striatal kinetics better than model 3. The parameters estimated using model 2 (four parameters) were in better agreement with those estimated by the nonlinear model (model 1) than those estimated using model 3 (three parameters). The use of a graphical approach gives estimates of the plasma-tissue fractional transport rate constant K1 and the net uptake constant K3 comparable to estimates using model 3 for both human and monkey studies.

• OSTI ID: 7068370
• Journal Information: Journal of Cerebral Blood Flow and Metabolism; (USA), Journal Name: Journal of Cerebral Blood Flow and Metabolism; (USA) Vol. 9:6; ISSN 0271-678X; ISSN JCBMD
• Country of Publication: United States
• Language: English

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550601* -- Medicine-- Unsealed Radionuclides in Diagnostics
62 RADIOLOGY AND NUCLEAR MEDICINE
AMINES
ANIMALS
AROMATICS
AUTONOMIC NERVOUS SYSTEM AGENTS
BETA DECAY RADIOISOTOPES
BETA-PLUS DECAY RADIOISOTOPES
BIOCHEMICAL REACTION KINETICS
BODY
BRAIN
CARDIOTONICS
CARDIOVASCULAR AGENTS
CENTRAL NERVOUS SYSTEM
COMPUTERIZED TOMOGRAPHY
DIAGNOSTIC TECHNIQUES
DOPAMINE
DRUGS
EMISSION COMPUTED TOMOGRAPHY
FLUORINE 18
FLUORINE ISOTOPES
HOURS LIVING RADIOISOTOPES
HYDROXY COMPOUNDS
IN VIVO
ISOMERIC TRANSITION ISOTOPES
ISOTOPES
KINETICS
LIGHT NUCLEI
MAMMALS
MAN
MATHEMATICAL MODELS
MEMBRANE PROTEINS
MONKEYS
NERVOUS SYSTEM
NEUROREGULATORS
NUCLEI
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
ORGANS
PHENOLS
POLYPHENOLS
POSITRON COMPUTED TOMOGRAPHY
PRIMATES
PROTEINS
RADIOISOTOPES
REACTION KINETICS
RECEPTORS
SYMPATHOMIMETICS
TOMOGRAPHY
VERTEBRATES