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

Conference · Sun Jan 01 00:00:00 EST 1984 · 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), Vol. 25:5; Conference: 31. annual meeting of the Society of Nuclear Medicine, Los Angeles, CA, USA, 5 Jun 1984
• Country of Publication: United States
• Language: English

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62 RADIOLOGY AND NUCLEAR MEDICINE
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POSITRON COMPUTED TOMOGRAPHY
FLUORINE 18
DIAGNOSTIC USES
TRACER TECHNIQUES
RECEPTORS
LABELLING
ALKYLATION
AMINES
AROMATICS
BLOOD PLASMA
DIAGRAMS
DRUGS
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INJECTION
LIGANDS
METABOLITES
RADIOACTIVITY
ANIMALS
BETA DECAY RADIOISOTOPES
BETA-PLUS DECAY RADIOISOTOPES
BIOLOGICAL MATERIALS
BLOOD
BODY
BODY FLUIDS
BRAIN
CENTRAL NERVOUS SYSTEM
CHEMICAL REACTIONS
COMPUTERIZED TOMOGRAPHY
DIAGNOSTIC TECHNIQUES
EMISSION COMPUTED TOMOGRAPHY
FLUORINE ISOTOPES
HOURS LIVING RADIOISOTOPES
INTAKE
ISOTOPE APPLICATIONS
ISOTOPES
LIGHT NUCLEI
MAMMALS
MATERIALS
MEMBRANE PROTEINS
NERVOUS SYSTEM
NUCLEI
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
ORGANS
PRIMATES
PROTEINS
RADIOISOTOPES
TOMOGRAPHY
USES
VERTEBRATES
550602* - Medicine- External Radiation in Diagnostics- (1980-)
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