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Method for detecting the cardiotoxicity of compounds

Assignee: Lantheus Medical Imaging Inc
•
Filing: 1993-02-26
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Granted: 1997-02-18
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Expires: 2013-02-26
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Abstract

Abstract The present invention provides methods of testing the cardiotoxicity of compounds and kits useful for the same.

Inventors

  • 👤 Paul D. Crane
  • 👤 Cesare Orlandi

Bibliographic Details

Application Number —
Jurisdiction US
Data Source google_patents
Last Synchronized 2026-11-09 22:27
CPC Classifications
G; G01; G01N; G01N33/00; G01N33/48; G01N33/50; G01N33/5005; G01N33/5008; G01N33/5014; Y; Y10; Y10S; Y10S435/00; Y10S435/968

Claims Analysis

Total Claims: 31
Claim 1
Independent Claim 65 words
A method of testing for cardiotoxicity of a compound comprising the steps of: labeling cells having a negative membrane potential with a labeled lipophilic cationic agent; homogenizing the labeled cells to provide a cell homogenate; incubating the cell homogenate with the compound to be tested; obtaining a mitochondrial fraction from the cell homogenate; measuring the amount of labeled lipophilic cationic agent in the mitochondrial fraction.
Claim 2
Independent Claim 65 words
A method of testing for cardiotoxicity of a compound comprising the steps of: labeling cells having a negative membrane potential with a labeled lipophilic cationic agent; homogenizing the labeled cells to provide a cell homogenate; incubating the cell homogenate with the compound to be tested; obtaining a mitochondrial fraction from the cell homogenate; measuring the amount of labeled lipophilic cationic agent in the mitochondrial fraction.
Claim 3
Dependent Claim 24 words
The method of claim 1 wherein the cells are labeled in vivo by intravenous injection of laboratory animals of the labeled lipophilic cationic agent.
Claim 4
Dependent Claim 23 words
The method of claim 1 wherein the cells are labeled in vitro by administration of the labeled lipophilic cationic agent to the cells.
Claim 5
Dependent Claim 15 words
The method of claim 1 wherein the cells are EJ, RT4, SKBR3 or MCF7 cells.
Claim 6
Dependent Claim 46 words
The method of claim 1 wherein the lipophilic cationic agent is labeled with a radiolabel selected from the group consisting of a radioactive isotope of carbon, hydrogen, iodine, technetium, ruthenium, cobalt, platinum, iron, osmium, iridium, tungsten, rhenium, chromium, molybdenum, manganese, nickel, rhodium, lead, niobium, and terbium.
Claim 7
Dependent Claim 27 words
The method of claim 5 wherein the radioactive isotope is selected from the group consisting of C-14, H-3, I-125, Tc-99m, Tc-99, Ru-97, Cr-51, Co-57, Re-188, and Os-191.
Claim 8
Dependent Claim 11 words
The method of claim 6 wherein the radioactive isotope is Tc-99m.
Claim 9
Dependent Claim 17 words
The method of claim 1 wherein the lipophilic cationic agent is labeled with a cationic lipophilic dye.
Claim 10
Dependent Claim 10 words
The method of claim 8 wherein the dye is rhodamine.
Claim 11
Independent Claim 84 words
A method of testing for cardiotoxicity of a compound comprising the steps of: labeling cells having a negative membrane potential with a labeled isonitrile having the formula where M is a label and R is a straight, branched, or cyclic chain C 1 -C 10 alkyl group; homogenizing the labeled cells to provide a cell homogenate; incubating the cell homogenate with the compound to be tested; obtaining a mitochondrial fraction from the cell homogenate; measuring the amount of labeled isonitrile in the mitochondrial fraction.
Claim 12
Independent Claim 84 words
A method of testing for cardiotoxicity of a compound comprising the steps of: labeling cells having a negative membrane potential with a labeled isonitrile having the formula where M is a label and R is a straight, branched, or cyclic chain C 1 -C 10 alkyl group; homogenizing the labeled cells to provide a cell homogenate; incubating the cell homogenate with the compound to be tested; obtaining a mitochondrial fraction from the cell homogenate; measuring the amount of labeled isonitrile in the mitochondrial fraction.
Claim 13
Dependent Claim 19 words
The method of claim 10 wherein the cells are labeled in vivo by intravenous injection of the labeled isonitrile.
Claim 14
Dependent Claim 21 words
The method of claim 10 wherein the cells are labeled in vitro by administration of the labeled isonitrile to the cells.
Claim 15
Dependent Claim 15 words
The method of claim 10 wherein the cells are EJ, RT4, SKBR3 or MCF7 cells.
Claim 16
Dependent Claim 45 words
The method of claim 10 wherein the labeled isonitrile is labeled with a radiolabel selected from the group consisting of a radioactive isotope of carbon, hydrogen, iodine, technetium, ruthenium, cobalt, platinum, iron, osmium, iridium, tungsten, rhenium, chromium, molybdenum, manganese, nickel, rhodium, lead, niobium, and terbium.
Claim 17
Dependent Claim 27 words
The method of claim 14 wherein the radioactive isotope is selected from the group consisting of C-14, H-3, I-125, Tc-99m, Tc-99, Ru-97, Cr-51, Co-57, Re-188, and Os-191.
Claim 18
Dependent Claim 11 words
The method of claim 15 wherein the radioactive isotope is Tc-99m.
Claim 19
Dependent Claim 17 words
The method of claim 10 wherein the lipophilic cationic agent is labeled with a cationic lipophilic dye.
Claim 20
Dependent Claim 10 words
The method of claim 17 wherein the dye is rhodamine.
Claim 21
Independent Claim 149 words
A method of testing for cardiotoxicity of a compound comprising the steps of: labeling cells having a negative membrane potential with a labeled ether-substituted isonitrile having the formula wherein M is a radionuclide, A is a straight or branched chain alkyl group and R is a straight or branched chain alkyl group, provided that the total number of carbon atoms in A plus R is 4 to 6, further provided that when the total number of carbon atoms in A plus R is 6, that the carbon atom alpha to the isonitrile group is a quaternary carbon, and still further provided that A is not (CH 2 ) 3 ; homogenizing labeled cells to provide a cell homogenate; incubating the cell homogenate with the compound to be tested; obtaining a mitochondrial fraction from the cell homogenate; and measuring the amount of labeled ether-substituted isonitrile released from the mitochondrial fraction.
Claim 22
Independent Claim 149 words
A method of testing for cardiotoxicity of a compound comprising the steps of: labeling cells having a negative membrane potential with a labeled ether-substituted isonitrile having the formula wherein M is a radionuclide, A is a straight or branched chain alkyl group and R is a straight or branched chain alkyl group, provided that the total number of carbon atoms in A plus R is 4 to 6, further provided that when the total number of carbon atoms in A plus R is 6, that the carbon atom alpha to the isonitrile group is a quaternary carbon, and still further provided that A is not (CH 2 ) 3 ; homogenizing labeled cells to provide a cell homogenate; incubating the cell homogenate with the compound to be tested; obtaining a mitochondrial fraction from the cell homogenate; and measuring the amount of labeled ether-substituted isonitrile released from the mitochondrial fraction.
Claim 23
Dependent Claim 23 words
The method of claim 19 wherein the cells are labeled in vivo by intravenous injection of laboratory animals of the labeled ether-substituted isonitrile.
Claim 24
Dependent Claim 22 words
The method of claim 19 wherein the cells are labeled in vitro by administration of the labeled ether-substituted isonitrile to the cells.
Claim 25
Dependent Claim 15 words
The method of claim 19 wherein the cells are EJ, RT4, SKBR3 or MCF7 cells.
Claim 26
Dependent Claim 45 words
The method of claim 19 wherein the ether-substituted isonitrile is labeled with a radiolabel selected from the group consisting of a radioactive isotope of carbon, hydrogen, iodine, technetium, ruthenium, cobalt, platinum, iron, osmium, iridium, tungsten, rhenium, chromium, molybdenum, manganese, nickel, rhodium, lead, niobium, and terbium.
Claim 27
Dependent Claim 27 words
The method of claim 23 wherein the radioactive isotope is selected from the group consisting of C-14, H-3, I-125, Tc-99m, Tc-99, Ru-97, Cr-51, Co-57, Re-188, and Os-191.
Claim 28
Dependent Claim 11 words
The method of claim 24 wherein the radioactive isotope is Tc-99m.
Claim 29
Dependent Claim 17 words
The method of claim 19 wherein the lipophilic cationic agent is labeled with a cationic lipophilic dye.
Claim 30
Dependent Claim 10 words
The method of claim 26 wherein the dye is rhodamine.
Claim 31
Dependent Claim 19 words
The method of claim 19 wherein the ether-substituted isonitrile is CNCH 2 C(CH 3 ) 2 OCH 3 .

References Cited (Backward Citations)

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