A comparison of (/sup 18/F)spiroperidol, (/sup 18/F)benperidol and (/sup 18/F) haloperidol kinetics in baboon brain

Conference · Sat Dec 31 23:00:00 EST 1983 · J. Nucl. Med.; (United States)

OSTI ID:6779330

Arnett, C D; Shiue, C Y; Wolf, A P; Fowler, J S; Logan, J

Neuroleptic receptor ligands, spiroperidol, benperidol and haloperidol were labeled with fluorine-18 by a nucleophilic aromatic substitution reaction of p-nitrobenzo-nitrile with /sup 18/F/sup -/ to produce p-(/sup 18/F)fluorobenzonitrile which was converted to p-(/sup 18/F)fluoro-y-chlorobutyrophenone and then alkylated with the appropriate amine to give (/sup 18/F)spiroperidol ((/sup 18/F)SP), (/sup 18/F)benperidol ((/sup 18/F)BEN), or (/sup 18/F)haloperidol ((/sup 18/F)HAL). Specific activity ranged from 3 to 6 Ci/..mu..mol. Anesthetized baboons were injected with 6-17 mCi of (/sup 18/F)-labeled tracer. Kinetic curves (striatum and cerebellum) were obtained from PETT scans up to 4 hr with each drug; (/sup 18/F)SP was studied to 8 hr. (/sup 18/F)SP and (/sup 18/F)BEN exhibited similar kinetics in striatum, with radioactivity concentration plateauing by 30 min after injection and remaining constant for the remainder of the study. These two compounds cleared rapidly from the cerebellum. (/sup 18/F)HAL showed a much different kinetic pattern in the striatum. Although it reached a higher striatal concentration (approx. =0.07% per ml vs. approx. = 0.02% per ml for (/sup 18/F)SP or (/sup 18/F)BEN), a peak occurred at 30 min after injection, followed by a decline almost as rapid as that in the cerebellum. Plasma analyses for (/sup 18/F)SP showed > 90% unchanged drug up to 5 min and approx. = 30% metabolites at 20 min after injection. Pretreatment with (+)-butaclamol abolished the selective distribution of (/sup 18/F)SP to the striatum in the four animals studied. Both (/sup 18/F)SP and (/sup 18/F)BEN may be suitable for PETT studies of neuroleptic receptors, but the in vivo kinetics of these compounds are markedly different from their in vitro receptor binding kinetics.

• Research Organization: Brookhaven National Lab., Upton, NY
• OSTI ID: 6779330
• Report Number(s): CONF-840619-
• Journal Information: J. Nucl. Med.; (United States), Journal Name: J. Nucl. Med.; (United States) Vol. 25:5; ISSN JNMEA
• Country of Publication: United States
• Language: English

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62 RADIOLOGY AND NUCLEAR MEDICINE
ALKYLATION
AMINES
ANIMALS
APES
AROMATICS
BETA DECAY RADIOISOTOPES
BETA-PLUS DECAY RADIOISOTOPES
BIOLOGICAL MATERIALS
BLOOD
BLOOD PLASMA
BODY
BODY FLUIDS
BRAIN
CENTRAL NERVOUS SYSTEM
CEREBELLUM
CHEMICAL REACTIONS
COMPUTERIZED TOMOGRAPHY
DIAGNOSTIC TECHNIQUES
DIAGNOSTIC USES
DIAGRAMS
DRUGS
EMISSION COMPUTED TOMOGRAPHY
FLUORINE 18
FLUORINE ISOTOPES
HOURS LIVING RADIOISOTOPES
IN VITRO
IN VIVO
INJECTION
INTAKE
ISOTOPE APPLICATIONS
ISOTOPES
LABELLING
LIGANDS
LIGHT NUCLEI
MAMMALS
MATERIALS
MEMBRANE PROTEINS
METABOLITES
NERVOUS SYSTEM
NUCLEI
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
ORGANS
POSITRON COMPUTED TOMOGRAPHY
PRIMATES
PROTEINS
RADIOACTIVITY
RADIOISOTOPES
RECEPTORS
TOMOGRAPHY
TRACER TECHNIQUES
USES
VERTEBRATES