Method for labeling antibodies with a metal ion
AssigneeCentocor, Inc.
InventorsKoon Y. Pak, Richard T. Dean, Jeffrey A. Mattis
Life of this patent
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Abstract
Methods for rapidly labeling sulfhydryl-containing antibodies or fragments with technetium or rhenium radioisotopes are disclosed. The method generally involves combining an aqueous mixture of the radiometal in an oxidized form, a reducing agent and a water-soluble polyhydroxycarbonylic acid ligand to form a stable complex of the radiometal in its reduced state and contacting the mixture with the sulfhydryl-containing antibody or fragment to produce a radiometal-labeled antibody or fragment.
Claims23
A method of directly labeling a sulfhydryl-containing antibody or antibody fragment with a radiometal selected from the group consisting of technetium-99m, rhenium-186, rhenium-188, rhenium-189 and rhenium-191, comprising the steps of:
- a. forming a mixture consisting essentially of:
- i) the radiometal;
- and
- ii) a reducing agent and a water-soluble polyhydroxycarboxylic ligand selected from the group consisting of:
- saccharic acid, arabonic acid and salts thereof, wherein the ligand is capable of complexing the radiometal to form a soluble radiometal-ligand complex;
- b. contacting the mixture with the sulfhydryl-containing antibody or antibody fragment under conditions sufficient for direct transfer of the radiometal to the antibody or fragment to occur to form a radiometal-labeled antibody or antibody fragment.
A method of labeling a Fab' fragment with technetium-99m, comprising the steps of:
- a. forming a mixture of:
- i) technetium-99m in an oxidized state;
- and
- ii) a composition consisting essentially of a reducing agent and a polyhydroxycarboxylic acid selected from the group consisting of:
- saccharic acid, arabonic acid and salts thereof;
- and
- b. contacting the mixture with an Fab' fragment to produce a Tc-99m labeled Fab' fragment.
A method of labeling a Fab' fragment with technetium-99m, comprising the steps of:
- a. reacting aqueous pertechnetate-99m with saccharic acid n the presence of a reducing agent to form a stabilized complex of the saccharic acid and technetium-99m in a reduced state;
- and thereafter, reacting a Fab' fragment with the complex to form a Tc-99m-labeled Fab' fragment.
A method for labeling a Fab' fragment with technetium-99m, comprising:
- a. adding sodium pertechnetate-99m to a first vial containing an aqueous solution of stannous reducing agent and saccharic acid or a salt thereof;
- and
- b. thereafter mixing the contents of the first vial with the contents of a second vial containing an aqueous solution of a Fab' fragment under non-oxidizing conditions.
A composition for directly radiolabeling antibodies or antibody fragments, comprising a mixture of a reducing agent and saccharic acid or a salt thereof.
A kit for radiolabeling an antibody or antibody fragment comprising:
- a. a vial containing a mixture of a reducing agent and a water soluble ligand selected from the group consisting of:
- saccharic acid, arabonic acid and salts thereof;
- and
- b. a vial containing Fab' fragment under nonoxidizing conditions.
Dependencies are inferred from the claim text.