Synthesis of carbon-11 labeled dexetimide and levetimide for studying muscarinic acetylcholine receptors

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

OSTI ID:6852451

Dannals, R F; Langstrom, B; Ravert, H T; Wilson, A A; Wagner, Jr, H N

The localization and quantitation of the muscarinic acetylcholine receptor (m-AChR) in the living human brain using a non-invasive method, such as positron emission tomography (PET), may provide valuable information about receptor changes which have been observed post mortem in patients with Huntington's chorea and Alzheimer's dementia, as well as normal brain mechanisms mediated by the m-AChR. Although quinuclidinyl benzilate has been radioiodinated and radiomethylatd, the former is not useful with PET and the latter does not penetrate the blood-brain barrier; therefore, the authors chose to radiolabel dexetimide, a ligand which labels m-AChR in vitro and in vivo, and levetimide, its inactive enantiomer. Carbon-11 labeled carbon dioxide is bubbled through a tetrahydrofuran (THF) solution of phenylmagnesium chloride (1 M, l ml) after which 2 mg of lithium aluminium hydride is added in THF (500 ..mu..l). After evaporation of the solvent, 48% hydriodic acid (l ml) is added and the solution is heated for 1 minute. Carbon-11 labeled benzyl iodide is extracted into methylene chloride, added to a solution of nor-benzyl dexetimide or levetimide, and heated for several minutes. Purification is accomplished using semi-preparative reverse phase high performance liquid chromatography (HPLC). Analytical HPLC is used to determine the radiochemical purity and specific activity.

• Research Organization: The Johns Hopkins Medical Institutions, Baltimore, MD
• OSTI ID: 6852451
• 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
550801* -- Morphology-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
62 RADIOLOGY AND NUCLEAR MEDICINE
ACETYLCHOLINE
AMINES
AMMONIUM COMPOUNDS
ANATOMY
ANIMALS
AUTONOMIC NERVOUS SYSTEM AGENTS
BETA DECAY RADIOISOTOPES
BETA-PLUS DECAY RADIOISOTOPES
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL LOCALIZATION
BODY
BRAIN
CARBON 11
CARBON ISOTOPES
CENTRAL NERVOUS SYSTEM
CHEMICAL PREPARATION
CHEMISTRY
CHROMATOGRAPHY
COMPUTERIZED TOMOGRAPHY
DIAGNOSTIC TECHNIQUES
DISTRIBUTION
DRUGS
EMISSION COMPUTED TOMOGRAPHY
ESTERS
EVEN-ODD NUCLEI
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
LABELLING
LIGHT NUCLEI
LIQUID COLUMN CHROMATOGRAPHY
MAMMALS
MAN
MEMBRANE PROTEINS
MINUTES LIVING RADIOISOTOPES
NERVOUS SYSTEM
NEUROREGULATORS
NUCLEI
ORGANIC COMPOUNDS
ORGANS
PARASYMPATHOMIMETICS
POSITRON COMPUTED TOMOGRAPHY
PRIMATES
PROTEINS
PURIFICATION
QUATERNARY COMPOUNDS
RADIOCHEMISTRY
RADIOISOTOPES
RADIORECEPTOR ASSAY
REACTION KINETICS
RECEPTORS
SEPARATION PROCESSES
SYNTHESIS
TISSUE DISTRIBUTION
TOMOGRAPHY
TRACER TECHNIQUES
VERTEBRATES