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Title: Positron emitter labeled enzyme inhibitors

Abstract

This invention involves a new strategy for imaging and mapping enzyme activity in the living human and animal body using positron emitter-labeled suicide enzyme inactivators or inhibitors which become covalently bound to the enzyme as a result of enzymatic catalysis. Two such suicide inactivators for monoamine oxidase have been labeled with carbon-11 and used to map the enzyme subtypes in the living human and animal body using PET. By using positron emission tomography to image the distribution of radioactivity produced by the body penetrating radiation emitted by carbon-11, a map of functionally active monoamine oxidase activity is obtained. Clorgyline and L-deprenyl are suicide enzyme inhibitors and irreversibly inhibit monoamine oxidase. When these inhibitors are labeled with carbon-11 they provide selective probes for monoamine oxidase localization and reactivity in vivo using positron emission tomography.

Inventors:
; ; ;
Publication Date:
OSTI Identifier:
5664820
Patent Number(s):
US 4913891; A
Application Number:
PPN: US 7-052921A; TRN: 90-024672
Assignee:
Dept. of Energy, Washington, DC NOV; NOV-90-022039; EDB-90-126025; ERA-15-043317
Resource Type:
Patent
Resource Relation:
Patent File Date: 22 May 1987
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; 62 RADIOLOGY AND NUCLEAR MEDICINE; ENZYME INHIBITORS; CHEMICAL COMPOSITION; ENZYMES; INHIBITION; POSITRON COMPUTED TOMOGRAPHY; LABELLED COMPOUNDS; AMINES; BIOCHEMICAL REACTION KINETICS; ENZYME ACTIVITY; COMPUTERIZED TOMOGRAPHY; DIAGNOSTIC TECHNIQUES; EMISSION COMPUTED TOMOGRAPHY; KINETICS; ORGANIC COMPOUNDS; REACTION KINETICS; TOMOGRAPHY; 550200* - Biochemistry; 550601 - Medicine- Unsealed Radionuclides in Diagnostics

Citation Formats

Fowler, J.S., MacGregor, R.R., Wolf, A.P., and Langstrom, B. Positron emitter labeled enzyme inhibitors. United States: N. p., 1990. Web.
Fowler, J.S., MacGregor, R.R., Wolf, A.P., & Langstrom, B. Positron emitter labeled enzyme inhibitors. United States.
Fowler, J.S., MacGregor, R.R., Wolf, A.P., and Langstrom, B. Tue . "Positron emitter labeled enzyme inhibitors". United States. doi:.
@article{osti_5664820,
title = {Positron emitter labeled enzyme inhibitors},
author = {Fowler, J.S. and MacGregor, R.R. and Wolf, A.P. and Langstrom, B.},
abstractNote = {This invention involves a new strategy for imaging and mapping enzyme activity in the living human and animal body using positron emitter-labeled suicide enzyme inactivators or inhibitors which become covalently bound to the enzyme as a result of enzymatic catalysis. Two such suicide inactivators for monoamine oxidase have been labeled with carbon-11 and used to map the enzyme subtypes in the living human and animal body using PET. By using positron emission tomography to image the distribution of radioactivity produced by the body penetrating radiation emitted by carbon-11, a map of functionally active monoamine oxidase activity is obtained. Clorgyline and L-deprenyl are suicide enzyme inhibitors and irreversibly inhibit monoamine oxidase. When these inhibitors are labeled with carbon-11 they provide selective probes for monoamine oxidase localization and reactivity in vivo using positron emission tomography.},
doi = {},
journal = {},
number = ,
volume = ,
place = {United States},
year = {Tue Apr 03 00:00:00 EDT 1990},
month = {Tue Apr 03 00:00:00 EDT 1990}
}
  • This invention involved a new strategy for imaging and mapping enzyme activity in the living human and animal body using positron emitter-labeled suicide enzyme inactivators or inhibitors which become covalently bound to the enzyme as a result of enzymatic catalysis. Two such suicide in activators for monoamine oxidase have been labeled with carbon-11 and used to map the enzyme subtypes in the living human and animal body using PET. By using positron emission tomography to image the distribution of radioactivity produced by the body penetrating radiation emitted by carbon-11, a map of functionally active monoamine oxidase activity is obtained. Clorgylinemore » and L-deprenyl are suicide enzyme inhibitors and irreversibly inhibit monoamine oxidase. When these inhibitors are labeled with carbon-11 they provide selective probes for monoamine oxidase localization and reactivity in vivo using positron emission tomography. 2 figs.« less
  • This invention involves a new strategy for imaging and mapping enzyme activity in the living human and animal body using positron emitter-labeled suicide enzyme inactivators or inhibitors which become covalently bound to the enzyme as a result of enzymatic catalysis. Two such suicide inactivators for monoamine oxidase have been labeled with carbon-11 and used to map the enzyme subtypes in the living human and animal body using PET. By using positron emission tomography to image the distribution of radioactivity produced by the body penetrating radiation emitted by carbon-11, a map of functionally active monoamine oxidase activity is obtained. Clorgyline andmore » L-deprenyl are suicide enzyme inhibitors and irreversibly inhibit monoamine oxidase. When these inhibitors are labeled with carbon-11 they provide selective probes for monoamine oxidase localization and reactivity in vivo using positron emission tomography.« less
  • A process for detecting the presence of an antigen in a specimen is described, which process comprises: contacting said specimen with a substrate coated with antibodies of said antigen, incubating the contacted substrate and washing the substrate; contacting the washed material of step with a hapten conjugated antibody against said antigen, incubating the so-contacted material and washing the so-incubated material; contacting the washed material of step with a radioactive material labeled or enzyme containing anti-hapten antibody, incubating the so-contacted material and washing the same; and effecting radioimmunoassay if said antibody is radioactive or enzyme labeled immunoassay if said antibody containsmore » an enzyme moiety. Quantitative determination of the antigen in the specimen is effected by comparing the counts of the radioimmunoassay or the concentration of enzyme against a standard as by photocolormetric methods.« less
  • This patent describes a water soluble enzyme-labeled antibody reagent comprising an antibody reagent and an enzyme covalently linked thereto through a bis-maleimidopolyalkyleneglycol bridge group covalently bound to sulfhydryl groups, the antibody reagent being IgG or an Fab or Fab' fragment thereof.
  • To evaluate the feasibility of probing the distribution of angiotensin-converting enzyme (ACE) in vivo using positron emission tomography (PET), 4-cis-(18F)fluorocaptopril (18FCAP) was prepared by the reaction of the triflate 2 with K18F/Kryptofix 222 in MeCN followed by hydrolysis (2 N NaOH). The synthesis time was 1 hr with an average radiochemical yield (EOS) of 12% and a specific activity of greater than 300 Ci/mmol. In vivo biodistribution in rats at 30 min after administration showed high uptakes into organs known to have high ACE concentration (lung, kidney and aorta) and faster clearance of 18FCAP for lung and kidney, compared tomore » the clearance from the aorta. When different amounts of unlabeled 4-cis-fluorocaptopril (SQ 25750) were coinjected in rats, a dose of greater than 5 micrograms/kg decreased the lung uptake by one-half while only 1 microgram/kg decreased the kidney uptake by one-half. In general, the binding in the four tissues studied was saturable with the expected capacity. 18FCAP was administered to a human and displaceable uptake observed in the lung and kidney. The results demonstrate the feasibility of probing ACE in vivo using PET.« less