3-(2'-( sup 18 F)fluoroethyl)spiperone: In vivo biochemical and kinetic characterization in rodents, nonhuman primates, and humans

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.1989.117· OSTI ID:7165138

Barrio, J R; Satyamurthy, N; Huang, S C; Keen, R E; Nissenson, C H; Hoffman, J M; Ackermann, R F; Bahn, M M; Mazziotta, J C; Phelps, M E ^[1]

---

1. UCLA School of Medicine (USA)

3-(2'-(18F)fluoroethyl)spiperone (FESP), a recently developed dopamine D2-receptor binding radiopharmaceutical, was used for dynamic characterization of dopamine-receptor binding in Macaca nemestrina monkeys and humans with positron emission tomography (PET). FESP in vitro binding properties to the dopamine receptor (IC50 = 1.5 nM) are similar to those of spiperone. Serial PET scans in monkeys after intravenous bolus injection of FESP revealed specific radioactivity accumulation in striatum (rich in dopamine D2-receptors), whereas radioactivity concentration declined after 20 min in frontal cortex (serotonin receptors) and more rapidly in cerebellum (nonspecific binding). Specific dopamine D2-receptor binding was saturated with increasing concentrations of radioligand (specific activity range: 1-10,000 Ci/mmol), was stereospecifically blocked with (+)butaclamol (0.5 mg/kg), and showed only partial displacement with spiperone (200 micrograms/kg, i.v. administration 90 min after FESP injection). From PET experiments with FESP in humans, it is possible to visualize accumulation of radioactivity in striatum in a manner similar to that observed in monkeys and, ex vivo, in rodents (adult male Sprague-Dawley rats). Biochemical analyses in rat brain revealed that the activity (approximately 90%) in striatum was unmodified FESP up to 4 h after injection. On the other hand, FESP was metabolized peripherally (rat greater than monkey greater than human), with only 11% of plasma radioactivity remaining as intact FESP in rodents and 54% in humans after 2 h. Based on these interspecies scaling pharmacokinetic data, it is unequivocal that FESP peripheral metabolites do not significantly contribute to the accumulated radioactivity in striatal tissue. Therefore, it is concluded that FESP is suitable for the quantitative estimation of dopamine D2-receptor sites using PET.

• OSTI ID: 7165138
• 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

Related Subjects

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