Synthesis and biodistribution of (C-11) labeled irreversible inhibitors of MAO A and B
Alterations in the enzyme monoamine oxidase (MAO) have been implicated in a number of diseases. Two types of MAO (A and B) have been identified by their substrate selectivity as well as their selective inhibition by the propargyl amines clorgyline (la) and L-deprenyl (lb). These inhibitors, which are substrates for MAO A and B respectively, deactivate the enzyme by becoming covalently or irreversibly attached to it, and so, if labeled with a positron emitter may provide selective probes for MAO localization and reactivity in vivo using PET. N-(C-11)methyl 1a and 1b have been synthesized. Synthesis time was 40 min with a radiochemical yield (EOB) of approx. = 20% and a specific activity of approx. = 200 mCi/..mu..mole (EOB). Differences in tissue distribution between control and 1a and 1b in pretreated mice demonstrated specific uptake and retention of each of these tracers to organs known to contain the specific MAO subtype. Centrifugation of brain homogenates showed selective binding of activity to particulate material following protein precipitation. The results support the premise of specific irreversible binding in vivo of 1a to type A and 1b to type B MAO and demonstrate the feasibility of using this approach for probing functional enzyme activity in vivo using PET.
- Research Organization:
- Chemistry Dept., Brookhaven National Lab., Upton, NY
- OSTI ID:
- 6856685
- 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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(/sup 11/C)clorgyline and (/sup 11/C)-L-deprenyl and their use in measuring functional monoamine oxidase activity in the brain using positron emission tomography
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59 BASIC BIOLOGICAL SCIENCES
62 RADIOLOGY AND NUCLEAR MEDICINE
AMINE OXIDASES
BETA DECAY RADIOISOTOPES
BETA-PLUS DECAY RADIOISOTOPES
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL LOCALIZATION
BNL
CARBON 11
CARBON ISOTOPES
CHEMICAL PREPARATION
CHEMICAL REACTION YIELD
COMPUTERIZED TOMOGRAPHY
DIAGNOSTIC TECHNIQUES
DISTRIBUTION
DRUGS
EMISSION COMPUTED TOMOGRAPHY
ENZYME INHIBITORS
ENZYMES
EVEN-ODD NUCLEI
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
LABELLED COMPOUNDS
LABELLING
LIGHT NUCLEI
MINUTES LIVING RADIOISOTOPES
MODIFICATIONS
NATIONAL ORGANIZATIONS
NUCLEI
OXIDOREDUCTASES
POSITRON COMPUTED TOMOGRAPHY
RADIOISOTOPES
RADIOPHARMACEUTICALS
REACTION KINETICS
SYNTHESIS
TISSUE DISTRIBUTION
TOMOGRAPHY
TRACER TECHNIQUES
US AEC
US DOE
US ERDA
US ORGANIZATIONS
YIELDS