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

Abstract

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 ofmore » 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.« less

Authors:
; ; ; ; ;
Publication Date:
Research Org.:
National Institutes of Health, Bethesda, MD
OSTI Identifier:
7034858
Report Number(s):
CONF-850611-
Journal ID: CODEN: JNMEA; TRN: 87-010367
Resource Type:
Conference
Resource Relation:
Journal Name: J. Nucl. Med.; (United States); Journal Volume: 26:5; Conference: 32. annual meeting of the Society of Nuclear Medicine, Houston, TX, USA, 2 Jun 1985
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; 37 INORGANIC, ORGANIC, PHYSICAL AND ANALYTICAL CHEMISTRY; ANTIDEPRESSANTS; CHEMICAL PREPARATION; LABELLING; FLUORINE 18; RADIOCHEMISTRY; RADIOPHARMACEUTICALS; BIOCHEMICAL REACTION KINETICS; CHEMICAL REACTION KINETICS; CHEMICAL REACTION YIELD; METABOLISM; OPIUM; ORGANIC FLUORINE COMPOUNDS; RECEPTORS; TISSUE DISTRIBUTION; ANALGESICS; BETA DECAY RADIOISOTOPES; BETA-PLUS DECAY RADIOISOTOPES; CENTRAL NERVOUS SYSTEM AGENTS; CENTRAL NERVOUS SYSTEM DEPRESSANTS; CHEMISTRY; DISTRIBUTION; DRUGS; FLUORINE ISOTOPES; HOURS LIVING RADIOISOTOPES; ISOTOPES; KINETICS; LABELLED COMPOUNDS; LIGHT NUCLEI; MEMBRANE PROTEINS; NARCOTICS; NUCLEI; ODD-ODD NUCLEI; ORGANIC COMPOUNDS; ORGANIC HALOGEN COMPOUNDS; PROTEINS; PSYCHOTROPIC DRUGS; RADIOISOTOPES; REACTION KINETICS; SYNTHESIS; YIELDS; 550201* - Biochemistry- Tracer Techniques; 550501 - Metabolism- Tracer Techniques; 400201 - Chemical & Physicochemical Properties

Citation Formats

Channing, M.A., Eckelman, W.C., Bennett, J.M., Burke, T.R. Jr., Rice, K.C., and Larson, S.M.. Radiosynthesis of F-18-3-acetylcyclofoxy: A high affinity opiate antagonist. United States: N. p., 1985. Web.
Channing, M.A., Eckelman, W.C., Bennett, J.M., Burke, T.R. Jr., Rice, K.C., & Larson, S.M.. Radiosynthesis of F-18-3-acetylcyclofoxy: A high affinity opiate antagonist. United States.
Channing, M.A., Eckelman, W.C., Bennett, J.M., Burke, T.R. Jr., Rice, K.C., and Larson, S.M.. 1985. "Radiosynthesis of F-18-3-acetylcyclofoxy: A high affinity opiate antagonist". United States. doi:.
@article{osti_7034858,
title = {Radiosynthesis of F-18-3-acetylcyclofoxy: A high affinity opiate antagonist},
author = {Channing, M.A. and Eckelman, W.C. and Bennett, J.M. and Burke, T.R. Jr. and Rice, K.C. and Larson, S.M.},
abstractNote = {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.},
doi = {},
journal = {J. Nucl. Med.; (United States)},
number = ,
volume = 26:5,
place = {United States},
year = 1985,
month = 5
}

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