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Title: Carbon-11 and radioiodinated derivatives of lysergic acid diethylamide: Ligands for the study of serotonin S2 receptors in vivo

Abstract

2-(/sup 125/1)-LSD binds selectively and with high affinity to serotonin S2 receptors in vitro. In the present study, the authors prepared 2-(/sup 123/1)-LSD as well as a carbon-11 labeled analog. They also characterized the in vivo binding of these tracers to receptor sites in mouse brain to assess their potential for tomographic imaging of S2 receptors in man. The temporal distribution of 2-(/sup 125/1)-LSD paralleled the density of S2 receptors. Regional selectivity was maximal after 15 minutes when tissue to cerebellum ratios were: frontal cortex (2.6), olfactory tubercles (2.4), striatum (2.3), and cortex (2.0). Preinjection of ketanserin, a potent S2 antagonist, inhibited binding. 2-(/sup 123/1)-LSD, prepared in 20% yield from LSD and electrophilic I-123, gave similar results in vivo and may be useful for SPECT studies. The authors then synthesized N1-((/sup 11/C)-Me)-2-Br-LSD (/sup 11/C-MBL) from (/sup 11/C)-methyl iodide and 2-Br-LSD for PET imaging trials. /sup 11/C-MBL was isolated by HPLC in high chemical and radiochemical purity within 30 minutes from E.O.B. The average radiochemical yield was 20% and the specific activity was determined by U.V. spectroscopy to be up to 1300Ci/mMol (E.O.S.). 11C-MBL showed greater regional selectivity in vivo in mouse brain than 2-(/sup 125/1)-LSD. After 30 minutes, peak tissuemore » to cerebellum ratios were: frontal cortex (5.4), olfactory tubercles (4.2), striatum (3.0), and cortex (2.8). Preinjection of ketanserin markedly inhibited /sup 11/C-MBL binding. /sup 11/C-MBL is a promising candidate for PET studies of S2 receptors.« less

Authors:
; ; ; ; ; ; ; ; ;
Publication Date:
Research Org.:
Johns Hopkins Univ. and Medical Institutions, Baltimore, MD
OSTI Identifier:
6760684
Alternate Identifier(s):
OSTI ID: 6760684
Report Number(s):
CONF-850611-
Journal ID: CODEN: JNMEA; TRN: 87-010644
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:
62 RADIOLOGY AND NUCLEAR MEDICINE; 59 BASIC BIOLOGICAL SCIENCES; CEREBELLUM; ANATOMY; CEREBRAL CORTEX; POSITRON COMPUTED TOMOGRAPHY; HALLUCINOGENS; BIOCHEMICAL REACTION KINETICS; LABELLING; LYSERGIC ACID; RADIOPHARMACEUTICALS; CHEMICAL PREPARATION; TISSUE DISTRIBUTION; RADIORECEPTOR ASSAY; SEROTONIN; RECEPTORS; AMIDES; CARBON 11; CAT SCANNING; HEAD; INHIBITION; LIGANDS; LIQUID COLUMN CHROMATOGRAPHY; METABOLISM; MICE; RADIOCHEMISTRY; TIME DEPENDENCE; TRACER TECHNIQUES; ALKALOIDS; AMINES; ANIMALS; AROMATICS; AUTONOMIC NERVOUS SYSTEM AGENTS; AZAARENES; AZOLES; BETA DECAY RADIOISOTOPES; BETA-PLUS DECAY RADIOISOTOPES; BODY; BODY AREAS; BRAIN; CARBON ISOTOPES; CARBOXYLIC ACIDS; CENTRAL NERVOUS SYSTEM; CENTRAL NERVOUS SYSTEM AGENTS; CEREBRUM; CHEMISTRY; CHROMATOGRAPHY; COMPUTERIZED TOMOGRAPHY; DIAGNOSTIC TECHNIQUES; DISTRIBUTION; DRUGS; EMISSION COMPUTED TOMOGRAPHY; EVEN-ODD NUCLEI; HETEROCYCLIC ACIDS; HETEROCYCLIC COMPOUNDS; HYDROXY COMPOUNDS; INDOLES; ISOTOPE APPLICATIONS; ISOTOPES; KINETICS; LABELLED COMPOUNDS; LIGHT NUCLEI; MAMMALS; MEMBRANE PROTEINS; MINUTES LIVING RADIOISOTOPES; NERVOUS SYSTEM; NEUROREGULATORS; NUCLEI; ORGANIC ACIDS; ORGANIC COMPOUNDS; ORGANIC NITROGEN COMPOUNDS; ORGANS; PROTEINS; PSYCHOTROPIC DRUGS; PYRROLES; RADIOISOTOPES; RADIOPROTECTIVE SUBSTANCES; REACTION KINETICS; RODENTS; SEPARATION PROCESSES; SYMPATHOMIMETICS; SYNTHESIS; TOMOGRAPHY; TRYPTAMINES; VERTEBRATES 550601* -- Medicine-- Unsealed Radionuclides in Diagnostics; 550801 -- Morphology-- Tracer Techniques

Citation Formats

Lever, J.R., Hartig, P.R., Wong, D.F., Scheffel, U., Dannals, R.F., Wilson, A.A., Ravert, H.T., Hoffman, B.J., Frost, J.J., and Burns, H.D. Carbon-11 and radioiodinated derivatives of lysergic acid diethylamide: Ligands for the study of serotonin S2 receptors in vivo. United States: N. p., 1985. Web.
Lever, J.R., Hartig, P.R., Wong, D.F., Scheffel, U., Dannals, R.F., Wilson, A.A., Ravert, H.T., Hoffman, B.J., Frost, J.J., & Burns, H.D. Carbon-11 and radioiodinated derivatives of lysergic acid diethylamide: Ligands for the study of serotonin S2 receptors in vivo. United States.
Lever, J.R., Hartig, P.R., Wong, D.F., Scheffel, U., Dannals, R.F., Wilson, A.A., Ravert, H.T., Hoffman, B.J., Frost, J.J., and Burns, H.D. Wed . "Carbon-11 and radioiodinated derivatives of lysergic acid diethylamide: Ligands for the study of serotonin S2 receptors in vivo". United States. doi:.
@article{osti_6760684,
title = {Carbon-11 and radioiodinated derivatives of lysergic acid diethylamide: Ligands for the study of serotonin S2 receptors in vivo},
author = {Lever, J.R. and Hartig, P.R. and Wong, D.F. and Scheffel, U. and Dannals, R.F. and Wilson, A.A. and Ravert, H.T. and Hoffman, B.J. and Frost, J.J. and Burns, H.D.},
abstractNote = {2-(/sup 125/1)-LSD binds selectively and with high affinity to serotonin S2 receptors in vitro. In the present study, the authors prepared 2-(/sup 123/1)-LSD as well as a carbon-11 labeled analog. They also characterized the in vivo binding of these tracers to receptor sites in mouse brain to assess their potential for tomographic imaging of S2 receptors in man. The temporal distribution of 2-(/sup 125/1)-LSD paralleled the density of S2 receptors. Regional selectivity was maximal after 15 minutes when tissue to cerebellum ratios were: frontal cortex (2.6), olfactory tubercles (2.4), striatum (2.3), and cortex (2.0). Preinjection of ketanserin, a potent S2 antagonist, inhibited binding. 2-(/sup 123/1)-LSD, prepared in 20% yield from LSD and electrophilic I-123, gave similar results in vivo and may be useful for SPECT studies. The authors then synthesized N1-((/sup 11/C)-Me)-2-Br-LSD (/sup 11/C-MBL) from (/sup 11/C)-methyl iodide and 2-Br-LSD for PET imaging trials. /sup 11/C-MBL was isolated by HPLC in high chemical and radiochemical purity within 30 minutes from E.O.B. The average radiochemical yield was 20% and the specific activity was determined by U.V. spectroscopy to be up to 1300Ci/mMol (E.O.S.). 11C-MBL showed greater regional selectivity in vivo in mouse brain than 2-(/sup 125/1)-LSD. After 30 minutes, peak tissue to cerebellum ratios were: frontal cortex (5.4), olfactory tubercles (4.2), striatum (3.0), and cortex (2.8). Preinjection of ketanserin markedly inhibited /sup 11/C-MBL binding. /sup 11/C-MBL is a promising candidate for PET studies of S2 receptors.},
doi = {},
journal = {J. Nucl. Med.; (United States)},
number = ,
volume = 26:5,
place = {United States},
year = {Wed May 01 00:00:00 EDT 1985},
month = {Wed May 01 00:00:00 EDT 1985}
}

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