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-; TRN: 87-010615
- Journal Information:
- J. Nucl. Med.; (United States), Vol. 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
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Related Subjects
59 BASIC BIOLOGICAL SCIENCES
37 INORGANIC
ORGANIC
PHYSICAL AND ANALYTICAL CHEMISTRY
AMINE OXIDASES
BIOCHEMICAL REACTION KINETICS
LABELLING
TISSUE DISTRIBUTION
ENZYME INHIBITORS
POSITRON COMPUTED TOMOGRAPHY
RADIOPHARMACEUTICALS
CHEMICAL PREPARATION
BIOLOGICAL LOCALIZATION
BNL
CARBON 11
CHEMICAL REACTION YIELD
ENZYMES
MODIFICATIONS
OXIDOREDUCTASES
TRACER TECHNIQUES
BETA DECAY RADIOISOTOPES
BETA-PLUS DECAY RADIOISOTOPES
CARBON ISOTOPES
COMPUTERIZED TOMOGRAPHY
DIAGNOSTIC TECHNIQUES
DISTRIBUTION
DRUGS
EMISSION COMPUTED TOMOGRAPHY
EVEN-ODD NUCLEI
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
LABELLED COMPOUNDS
LIGHT NUCLEI
MINUTES LIVING RADIOISOTOPES
NATIONAL ORGANIZATIONS
NUCLEI
RADIOISOTOPES
REACTION KINETICS
SYNTHESIS
TOMOGRAPHY
US AEC
US DOE
US ERDA
US ORGANIZATIONS
YIELDS
550601* - Medicine- Unsealed Radionuclides in Diagnostics
550201 - Biochemistry- Tracer Techniques
400201 - Chemical & Physicochemical Properties