Radiosynthesis of F-18-3-acetylcyclofoxy: A high affinity opiate antagonist

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

OSTI ID:7034858

Channing, M A; Eckelman, W C; Bennett, J M; Burke, Jr, T R; Rice, K C; Larson, S M

A convenient method for the preparation of F-18-3-acetylcyclofoxy (3-acetyl-6-deoxy-6-beta-F-18-fluoronaltrexone was developed. The method uses reactor-produced F-18-fluoride as its tetraethylammonium salt. F-18 fluoride is produced at the National Bureau of Standards nuclear reactor by the Li-6(n,..cap alpha..)H-3, 0-16(H-3,n) F-18 nuclear reaction. A sealed quartz tube containing enriched lithium carbonate (0.4 g) was irradiated in a neutron flux of 1.1 x 10/sup 14/ n/cm/sup 2//s for 2h to produce 80 mCi. The lithium is removed by cation exchange resin. The fluoride is then adsorbed on a strong anion exchange column which is rinsed to remove H-3 and any remaining cations. The F-18 is then eluted with tetraethylammonium hydroxide to produce tetraethylammonium fluoride (TEAF). The triflate of 3-acetyl-6-alpha-naltrexol, synthesized by reaction of the alcohol with trifluoromethanesulfonic anhydride was added in anhydrous acetonitrile to the dry F-18 TEAF containing 0.2 ..mu..mol F-19 TEAF. The mixture was refluxed for 15 minutes after which the product was purified by reversed phase chromatography. F-18-acetylcyclofoxy was prepared in 35% radiochemical yield. About 55% of the F-18 was lost by decay (36%) and by incomplete transfer (19%). The specific activity of the final product was approximately 50 Ci/mmol but the effective specific activity was approximately 25 Ci/mmol. Visualization of the basal ganglia in baboons was possible using PET. F-18 3-acetylcyclofoxy is the first positron-emitting opiate for which the active and inactive forms of naloxone were used to unequivocially demonstrate stereospecific displacement from opiate receptor-rich regions.

• Research Organization: National Institutes of Health, Bethesda, MD
• OSTI ID: 7034858
• 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
550201* -- Biochemistry-- Tracer Techniques
550501 -- Metabolism-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ANALGESICS
ANTIDEPRESSANTS
BETA DECAY RADIOISOTOPES
BETA-PLUS DECAY RADIOISOTOPES
BIOCHEMICAL REACTION KINETICS
CENTRAL NERVOUS SYSTEM AGENTS
CENTRAL NERVOUS SYSTEM DEPRESSANTS
CHEMICAL PREPARATION
CHEMICAL REACTION KINETICS
CHEMICAL REACTION YIELD
CHEMISTRY
DISTRIBUTION
DRUGS
FLUORINE 18
FLUORINE ISOTOPES
HOURS LIVING RADIOISOTOPES
ISOTOPES
KINETICS
LABELLED COMPOUNDS
LABELLING
LIGHT NUCLEI
MEMBRANE PROTEINS
METABOLISM
NARCOTICS
NUCLEI
ODD-ODD NUCLEI
OPIUM
ORGANIC COMPOUNDS
ORGANIC FLUORINE COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
PROTEINS
PSYCHOTROPIC DRUGS
RADIOCHEMISTRY
RADIOISOTOPES
RADIOPHARMACEUTICALS
REACTION KINETICS
RECEPTORS
SYNTHESIS
TISSUE DISTRIBUTION
YIELDS