In vivo binding of spiperone and N-methylspiperone to dopaminergic and serotonergic sites in the rat brain: Multiple modeling and implications for PET scanning

Journal Article · Tue May 01 00:00:00 EDT 1990 · Journal of Cerebral Blood Flow and Metabolism; (USA)

DOI:https://doi.org/10.1038/jcbfm.1990.58· OSTI ID:6743756

Swart, J A; van der Werf, J F; Wiegman, T; Paans, A M; Vaalburg, W; Korf, J ^[1]

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1. Univ. of Groningen (Netherlands)

Equilibrium models are derived and applied to in vivo binding of spiperone in the rat brain. The models express the concentration of the ligand in the striatum and frontal cortex as a function of the accumulation in the cerebellum. The models differ with respect to the description of specific binding. Nonlinear regression analysis shows that the in vivo specific binding of 3H-labeled spiperone in the frontal cortex (mainly serotonergic) can be described by a noninteracting sites model, whereas the specific binding in the striatum (mainly dopaminergic) can best be described by models that lead to sigmoid saturation curves. These results were tested and partly confirmed by determining the region-of-interest/cerebellar radioactivity ratio of {sup 11}C-labeled N-methylspiperone, with and without pretreatment with haloperidol. The estimated Bmax was 32 fmol/mg wet tissue in the frontal cortex and approximately 90 fmol/mg wet tissue in the striatum. The free plus nonspecific binding of spiperone was similar in the frontal cortex but lower in the striatum than in the cerebellum. The occurrence of sigmoidicity can be best explained by the existence of high-affinity/low-capacity sites in the cerebellum rather than mutual interactions of striatal sites. The consequence of the present analysis for positron emission tomography is that the striatal/cerebellar activity ratio is not an accurate parameter of specific binding features at tracer doses of spiperone or N-methylspiperone.

• OSTI ID: 6743756
• Journal Information: Journal of Cerebral Blood Flow and Metabolism; (USA), Journal Name: Journal of Cerebral Blood Flow and Metabolism; (USA) Vol. 10:3; ISSN 0271-678X; ISSN JCBMD
• Country of Publication: United States
• Language: English

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59 BASIC BIOLOGICAL SCIENCES
62 RADIOLOGY AND NUCLEAR MEDICINE
AMINES
ANATOMY
ANIMALS
AROMATICS
AUTONOMIC NERVOUS SYSTEM AGENTS
AZAARENES
AZOLES
BETA DECAY RADIOISOTOPES
BETA-PLUS DECAY RADIOISOTOPES
BIOCHEMICAL REACTION KINETICS
BODY
BRAIN
CARBON 11
CARBON ISOTOPES
CARDIOTONICS
CARDIOVASCULAR AGENTS
CENTRAL NERVOUS SYSTEM
CEREBELLUM
CEREBRAL CORTEX
CEREBRUM
COMPUTERIZED TOMOGRAPHY
DIAGNOSTIC TECHNIQUES
DIAGNOSTIC USES
DISTRIBUTION
DOPAMINE
DRUGS
EMISSION COMPUTED TOMOGRAPHY
EVEN-ODD NUCLEI
HETEROCYCLIC COMPOUNDS
HYDROGEN COMPOUNDS
HYDROXY COMPOUNDS
INDOLES
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
LIGHT NUCLEI
MAMMALS
MEMBRANE PROTEINS
MINUTES LIVING RADIOISOTOPES
NERVOUS SYSTEM
NEUROREGULATORS
NUCLEI
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PHENOLS
POLYPHENOLS
POSITRON COMPUTED TOMOGRAPHY
PROTEINS
PYRROLES
RADIOISOTOPES
RADIOPROTECTIVE SUBSTANCES
RATS
REACTION KINETICS
RECEPTORS
RODENTS
SEROTONIN
SPIPERONE
SYMPATHOMIMETICS
TISSUE DISTRIBUTION
TOMOGRAPHY
TRACER TECHNIQUES
TRITIUM COMPOUNDS
TRYPTAMINES
USES
VERTEBRATES