F-18 labeled 3-fluorodiazepam

Conference · Wed May 01 04:00:00 EDT 1985 · J. Nucl. Med.; (United States)

OSTI ID:6856672

Luxen, A; Barrio, J R; Bida, G T; Satyamurthy, N; Phelps, M E

3-Fluorodiazepam is a new and potent antianxiety agent with prolonged action. The authors found that molecular fluorine (0.5% in Ne) reacts cleanly with diazepam in freon or chloroform at room temperature to produce 3-fluorodiazepam in good yields. Successful syntheses have employed 2:1 to 5:1 molar ratios diazepam: fluorine to minimize the formation of byproducts. (/sup 18/F) 3-Fluorodiazepam, a potential candidate for PET studies, (specific activity 3-5 Ci/mmol) has been synthesized from /sup 18/F-F/sub 2/ using the same procedure, followed by column chromatographic purification (Silicagel, dichloromethane: ethyl acetate, 5:1) with a radiochemical yield of 12-20% (50% maximum) and a chemical and radiochemical purity >99% as judged by reversed-phase high pressure liquid chromatography analysis (Ultrasyl octyl column, 10 ..mu.. m, 4.6 x 250 mm i.d., 60% MeOH 40% water; flow rate, 1.0 ml/min; retention time for (/sup 18/F) fluorodiazepam, 11.4 min; for diazepam, 13.5 min; radioactivity and ultraviolet detectors). Lower radiochemical yields (5-7%), and significant formation of by-products were observed when (/sup 18/F)acetylhypofluorite, prepared in the gasphase, was used as the reagent. Readily accessible routes to /sup 18/F-labeled benzodiazepines of higher specific activity were also investigated. Approaches to the synthesis of high specific activity (>200 Ci/mmol) (/sup 18/F)3-fluorodiazepam involve nucleophilic displacement at carbon-3 (e.g. from 3-chlorodiazepam) with (/sup 18/F)fluoride ion. The results presented here demonstrate the synthetic accessibility of /sup 18/F-labeled benzodiazepines for application in neurotransmitter ligand studies with PET.

• Research Organization: UCLA School of Medicine, Los Angeles, CA 90024
• OSTI ID: 6856672
• Report Number(s): CONF-850611-
• Conference Information: Journal Name: J. Nucl. Med.; (United States) Journal Volume: 26:5
• Country of Publication: United States
• Language: English

Related Subjects

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY
400201 -- Chemical & Physicochemical Properties
550601* -- Medicine-- Unsealed Radionuclides in Diagnostics
62 RADIOLOGY AND NUCLEAR MEDICINE
ANTIDEPRESSANTS
BETA DECAY RADIOISOTOPES
BETA-PLUS DECAY RADIOISOTOPES
CENTRAL NERVOUS SYSTEM AGENTS
CHEMICAL PREPARATION
CHEMICAL REACTION KINETICS
CHEMICAL REACTION YIELD
COMPUTERIZED TOMOGRAPHY
DIAGNOSTIC TECHNIQUES
DISTRIBUTION
DRUGS
EMISSION COMPUTED TOMOGRAPHY
FLUORINE 18
FLUORINE ISOTOPES
HOURS LIVING RADIOISOTOPES
ISOTOPES
KINETICS
LABELLED COMPOUNDS
LABELLING
LIGANDS
LIGHT NUCLEI
METABOLISM
NUCLEI
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
ORGANIC FLUORINE COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
PERFORMANCE
POSITRON COMPUTED TOMOGRAPHY
PSYCHOTROPIC DRUGS
RADIOISOTOPES
RADIOPHARMACEUTICALS
REACTION KINETICS
SYNTHESIS
TISSUE DISTRIBUTION
TOMOGRAPHY
YIELDS