Radiosynthesis and pharmacokinetics of high specific activity /sup 75,77/Br-bromperidol, a potent butyrophenone neuroleptic

Conference · Sun Jan 01 04:00:00 EST 1984 · J. Nucl. Med.; (United States)

OSTI ID:6586713

Moerlein, S M; Stocklin, G

Bromperidol, 4-(4-(4-bromophenyl)-4-hydroxypiperidino)-4'- fluorobutyrophenone, is a potent neuroleptic which has found clinical use in the treatment of schizophrenia. Of the major dopaminergic receptor-binding ligands, bromperidol has the greatest specificity for binding to cerebral dopamine receptors (K/sub i/ = 3.7 nM) relative to competitive cerebral serotonin (K/sub i/ = 26 nM), ..cap alpha..-adrenergic (K/sub i/ = 100 nM) or histamine (K/sub i/ = 700 nM) receptors. The authors have therefore prepared bromperidol labelled with no-carrier-added (n.c.a.) /sup 75/Br (t/sub 1/2/ = 1.6 hr ..beta../sup +/) or /sup 77/Br (t/sub 1/2/ = 52 hr EC) for evaluation as a radiopharmaceutical for mapping cerebral dopamine receptor areas with PECT technology, as well as for non-invasive pharmacodynamic studies in man with conventional nuclear medicine equipment. 4-(4-(4-trimethylstannylphenyl)-4-hydroxypiperidino)-4'- fluorobutyrophenone, TMSn-P, was synthesized in 40% chemical yield by reaction of trimethylstannyl sodium with bromperidol. TMSn-P was purified by preparative HPLC and characterized by /sup 1/H-NMR and GC-MS. TMSn-P was radiobrominated in methanol using n.c.a. /sup 75/Br/sup -/ or /sup 77/Br/sup -/ and dichloramine-T as oxidizing agent. Product /sup 75,77/Br-bromperidol was separated from impurities, including chlorinated side-product halo-peridol, using HPLC (RP-18; MeOH/H/sub 2/O/Et/sub 3/N = 70/30/0.3). For a reaction time of 5 minutes, and an overall radiopharmaceutical production time of 30 minutes, /sup 75,77/Br-bromperidol was obtained in physiological saline solution with 40% radiochemical yield and a specific activity > 10,000 Ci/mmole. The pharmacokinetics in rodents and PECT studies in primates using /sup 75,77/Br-bromperidol are compared with that of previously-reported /sup 75,77/Br-brombenperidol.

• Research Organization: Kernforschungsanlage, Juelich
• OSTI ID: 6586713
• Report Number(s): CONF-840619-
• Conference Information: Journal Name: J. Nucl. Med.; (United States) Journal Volume: 25:5
• Country of Publication: United States
• Language: English

Related Subjects

38 RADIATION CHEMISTRY, RADIOCHEMISTRY, AND NUCLEAR CHEMISTRY
400702 -- Radiochemistry & Nuclear Chemistry-- Properties of Radioactive Materials
550801* -- Morphology-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
AMINES
ANIMALS
AROMATICS
AUTONOMIC NERVOUS SYSTEM AGENTS
BETA DECAY RADIOISOTOPES
BETA-PLUS DECAY RADIOISOTOPES
BIOCHEMICAL REACTION KINETICS
BODY
BRAIN
BROMINE 75
BROMINE ISOTOPES
CARDIOTONICS
CARDIOVASCULAR AGENTS
CENTRAL NERVOUS SYSTEM
CENTRAL NERVOUS SYSTEM AGENTS
CHEMICAL PREPARATION
CHEMISTRY
CHROMATOGRAPHY
COMPARATIVE EVALUATIONS
COMPUTERIZED TOMOGRAPHY
COUNTING TECHNIQUES
DIAGNOSTIC TECHNIQUES
DISTRIBUTION
DOPAMINE
DRUGS
ELECTRON CAPTURE RADIOISOTOPES
EMISSION COMPUTED TOMOGRAPHY
EVALUATION
HOURS LIVING RADIOISOTOPES
HYDROXY COMPOUNDS
INTERMEDIATE MASS NUCLEI
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
LABELLED COMPOUNDS
LABELLING
LIQUID COLUMN CHROMATOGRAPHY
MAMMALS
MEMBRANE PROTEINS
NERVOUS SYSTEM
NEUROREGULATORS
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANS
PHENOLS
POLYPHENOLS
PRIMATES
PROTEINS
PSYCHOTROPIC DRUGS
RADIOCHEMISTRY
RADIOISOTOPE SCANNING
RADIOISOTOPES
RADIOPHARMACEUTICALS
RADIORECEPTOR ASSAY
REACTION KINETICS
RECEPTORS
RODENTS
SCINTISCANNING
SEPARATION PROCESSES
SINGLE PHOTON EMISSION COMPUTED TOMOGRAPHY
SYMPATHOMIMETICS
SYNTHESIS
TISSUE DISTRIBUTION
TOMOGRAPHY
TRACER TECHNIQUES
VERTEBRATES