Radiosynthesis and pharmacokinetics of high specific activity /sup 75,77/Br-bromperidol, a potent butyrophenone neuroleptic
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-; TRN: 87-022320
- 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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38 RADIATION CHEMISTRY, RADIOCHEMISTRY, AND NUCLEAR CHEMISTRY
BRAIN
RADIORECEPTOR ASSAY
SCINTISCANNING
SINGLE PHOTON EMISSION COMPUTED TOMOGRAPHY
PSYCHOTROPIC DRUGS
BIOCHEMICAL REACTION KINETICS
CHEMICAL PREPARATION
LABELLING
TISSUE DISTRIBUTION
BROMINE 75
COMPARATIVE EVALUATIONS
DOPAMINE
EVALUATION
LIQUID COLUMN CHROMATOGRAPHY
PRIMATES
RADIOCHEMISTRY
RADIOPHARMACEUTICALS
RECEPTORS
RODENTS
AMINES
ANIMALS
AROMATICS
AUTONOMIC NERVOUS SYSTEM AGENTS
BETA DECAY RADIOISOTOPES
BETA-PLUS DECAY RADIOISOTOPES
BODY
BROMINE ISOTOPES
CARDIOTONICS
CARDIOVASCULAR AGENTS
CENTRAL NERVOUS SYSTEM
CENTRAL NERVOUS SYSTEM AGENTS
CHEMISTRY
CHROMATOGRAPHY
COMPUTERIZED TOMOGRAPHY
COUNTING TECHNIQUES
DIAGNOSTIC TECHNIQUES
DISTRIBUTION
DRUGS
ELECTRON CAPTURE RADIOISOTOPES
EMISSION COMPUTED TOMOGRAPHY
HOURS LIVING RADIOISOTOPES
HYDROXY COMPOUNDS
INTERMEDIATE MASS NUCLEI
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
LABELLED COMPOUNDS
MAMMALS
MEMBRANE PROTEINS
NERVOUS SYSTEM
NEUROREGULATORS
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANS
PHENOLS
POLYPHENOLS
PROTEINS
RADIOISOTOPE SCANNING
RADIOISOTOPES
REACTION KINETICS
SEPARATION PROCESSES
SYMPATHOMIMETICS
SYNTHESIS
TOMOGRAPHY
TRACER TECHNIQUES
VERTEBRATES
550801* - Morphology- Tracer Techniques
400702 - Radiochemistry & Nuclear Chemistry- Properties of Radioactive Materials