Carbon-11 and radioiodinated derivatives of lysergic acid diethylamide: Ligands for the study of serotonin S2 receptors in vivo
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.
- Research Organization:
- Johns Hopkins Univ. and Medical Institutions, Baltimore, MD
- OSTI ID:
- 6760684
- Report Number(s):
- CONF-850611-
- Journal Information:
- J. Nucl. Med.; (United States), Journal Name: J. Nucl. Med.; (United States) Vol. 26:5; ISSN JNMEA
- Country of Publication:
- United States
- Language:
- English
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550801 -- Morphology-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
62 RADIOLOGY AND NUCLEAR MEDICINE
ALKALOIDS
AMIDES
AMINES
ANATOMY
ANIMALS
AROMATICS
AUTONOMIC NERVOUS SYSTEM AGENTS
AZAARENES
AZOLES
BETA DECAY RADIOISOTOPES
BETA-PLUS DECAY RADIOISOTOPES
BIOCHEMICAL REACTION KINETICS
BODY
BODY AREAS
BRAIN
CARBON 11
CARBON ISOTOPES
CARBOXYLIC ACIDS
CAT SCANNING
CENTRAL NERVOUS SYSTEM
CENTRAL NERVOUS SYSTEM AGENTS
CEREBELLUM
CEREBRAL CORTEX
CEREBRUM
CHEMICAL PREPARATION
CHEMISTRY
CHROMATOGRAPHY
COMPUTERIZED TOMOGRAPHY
DIAGNOSTIC TECHNIQUES
DISTRIBUTION
DRUGS
EMISSION COMPUTED TOMOGRAPHY
EVEN-ODD NUCLEI
HALLUCINOGENS
HEAD
HETEROCYCLIC ACIDS
HETEROCYCLIC COMPOUNDS
HYDROXY COMPOUNDS
INDOLES
INHIBITION
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
LABELLED COMPOUNDS
LABELLING
LIGANDS
LIGHT NUCLEI
LIQUID COLUMN CHROMATOGRAPHY
LYSERGIC ACID
MAMMALS
MEMBRANE PROTEINS
METABOLISM
MICE
MINUTES LIVING RADIOISOTOPES
NERVOUS SYSTEM
NEUROREGULATORS
NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
POSITRON COMPUTED TOMOGRAPHY
PROTEINS
PSYCHOTROPIC DRUGS
PYRROLES
RADIOCHEMISTRY
RADIOISOTOPES
RADIOPHARMACEUTICALS
RADIOPROTECTIVE SUBSTANCES
RADIORECEPTOR ASSAY
REACTION KINETICS
RECEPTORS
RODENTS
SEPARATION PROCESSES
SEROTONIN
SYMPATHOMIMETICS
SYNTHESIS
TIME DEPENDENCE
TISSUE DISTRIBUTION
TOMOGRAPHY
TRACER TECHNIQUES
TRYPTAMINES
VERTEBRATES