EP0083129A1
Expired / Lapsed
EP
⏱️ 0.0 years remaining
Method of preparing radionuclide-labelled proteins, in particular antibodies or antibody fragments
Assignee: Mallinckrodt Diagnostica Holland BV
•
Filing: 1982-12-14
•
Granted: —
•
Expires: 2002-12-14
Abstract
Abstract The invention relates to a method of preparing radionuclide-labelled proteins which are unstable at a pH lower than the physiological pH, in particular antibodies or antibody fragments, by reacting a protein which is provided with chelating group derived from Desferrioxamine, 8-hydroxyquinoline, imino triacetic acid-containing chelating agents, or imino diacetic acid-containing chelating agents, such as ethylenediamine tetracetic acid, diethylene triamine pentacetic acid or diaminocyclohexyl tetracetic acid, or salts hereof, or a chelating peptide or polypeptide such as transferrine, at a pH from 4 to 9, with a solution of an oxinate, a carboxylate, a dithiocarboxylate, an enolate, or a mixture thereof, of a radionuclide selected from the group consisting of radioactive indium, radioactive gallium, lead-203, ruthenium-97, mercury-197 and thallium(III)-201. The invention also relates to the labelled proteins thus obtained, to a radiopharmaceutical composition comprising said lebelled proteins, to the use of said composition for performing a radiodiagnostic examination, and to a kit for performing such an examination.
Inventors
- 👤 Wilhelmus Theodorus Goedemans
Bibliographic Details
Application Number
—
Jurisdiction
EP
Data Source
google_patents
Last Synchronized
2026-10-23 08:37
CPC Classifications
A; A61; A61K; A61K51/00; A61K51/02; A61K51/04; A61K51/08; A61K51/10; A61K51/1093; A61K2123/00
Claims Analysis
Total Claims: 13
Claim 1
Independent Claim
130 words
A method of preparing radionuclide-labelled proteins which are unstable at a pH lower than the physiological pH, in particular antibodies or antibody fragments, by reacting a protein which is provided with chelating groups, derived from Desferrioxamine, 8-hydroxyquinoline, iminotriacetic acid-containing chelating agents, or imino diacetic acid-containing chelating agents, such as ethylene diamine tetracetic acid, diethylene triamine pentacetic acid or diaminocyclohexyl tetracetic acid, or salts hereof, or a chelating peptide or polypeptide such as transferrine, with a solution of a-oompound of a radionuclide selected from the group consisting of radioactive indium, radio--active gallium, lead-203, ruthenium-97, mercury-197 and thallium-(III)-201, characterized in that the reaction is carried out at a pH from 4 to 9 with a solution of an oxinate, a carboxylate, a dithiocarboxylate, an enolate or a mixture thereof of the radionuclide.
Claim 2
Independent Claim
130 words
A method of preparing radionuclide-labelled proteins which are unstable at a pH lower than the physiological pH, in particular antibodies or antibody fragments, by reacting a protein which is provided with chelating groups, derived from Desferrioxamine, 8-hydroxyquinoline, iminotriacetic acid-containing chelating agents, or imino diacetic acid-containing chelating agents, such as ethylene diamine tetracetic acid, diethylene triamine pentacetic acid or diaminocyclohexyl tetracetic acid, or salts hereof, or a chelating peptide or polypeptide such as transferrine, with a solution of a-oompound of a radionuclide selected from the group consisting of radioactive indium, radio--active gallium, lead-203, ruthenium-97, mercury-197 and thallium-(III)-201, characterized in that the reaction is carried out at a pH from 4 to 9 with a solution of an oxinate, a carboxylate, a dithiocarboxylate, an enolate or a mixture thereof of the radionuclide.
Claim 3
Dependent Claim
101 words
A method as claimed in Claim 1, characterized in that the radionuclide is used in the form of an oxinate with 8-hydroxyquinoline or a derivative hereof, a carboxylate with oxalic acid, malonic acid, succinic acid, maleic acid, orthophthalic acid, malic acid, lactic acid, tartaric acid, citric acid, ascorbic acid, salicylic acid, iminodiacetic acid, iminotriacetic acid, or a derivative of any of these acids, a dithiocarboxylate with a dithiocarbamic acid, a dithiocarboxylic acid, or a derivative hereof, or an enolate with acetyl acetone, furoyl acetone, thenoyl acetone, benzoyl acetone, dibenzoyl methane, tropo lone, pyrithiore, or a derivative of any of these diketones.
Claim 4
Dependent Claim
28 words
A method as claimed in Claim 1 or 2, characterized in that a compound of indium-111, gallium-67, lead-203, or ruthenium-97 is used as a compound of a radionuclide.
Claim 5
Independent Claim
29 words
A method as claimed in any of the preceding Claims, characterized in that the reaction is carried out at a pH of 6 to 7.5, preferably at physiological pH.
Claim 6
Independent Claim
32 words
A method as claimed in any of the preceding Claims, characterized in that a protein is used which is provided with chelating groups derived from diethylene triamine pentacetic acid or salts hereof.
Claim 7
Independent Claim
33 words
A method as claimed in any of the preceding Claims, characterized in that the radionuclide is used in the form of a complex with 8-hydroxyquinoline, acetyl acetone, citric acid, or a derivative hereof.
Claim 8
Dependent Claim
21 words
Radionuclide-labelled proteins, in particular antibodies or antibody fragments, obtained by using the method as claimed in any of the preceding Claims.
Claim 9
Dependent Claim
47 words
A radiopharmaceutical composition which, in addition to a liquid carrier material which is acceptable to the body, comprises radionuclide-labelled proteins, in particular antibodies or antibody fragments, characterized in that the composition comprises radionuclide-labelled proteins obtained by using the method as claimed in any of the Claims 1-6.
Claim 10
Dependent Claim
69 words
A method of performing a radiodiagnostic examination, characterized in that the composition as claimed in Claim 8, if desired after dilution with a liquid which is acceptable to the body, is administered to a living being in a quantity from 100 µCi to 10 mCi, preferably from 0.5 to 3 mCi per 70 kg of body weight, and the radioactive radiation emitted by the living being is then recorded.
Claim 11
Dependent Claim
108 words
A kit for performing a radiodiagnostic examination comprising (1) a protein which is provided with chelating groups derived from Desferrioxamine, 8-hydroxyquinoline, iminotriacetic acid-containing chelating agents, or iminodiacetic acid-containing chelating agents such as ethylenediamine tetracetic acid, diethylenetriamine pentacetic acid or diaminocyclohexyl tetracetic acid, or salts hereof, or a chelating peptide or polypeptide such as transferring,whether or not in the dry,state, (2) a solution of an oxinate, a carboxylate, a dithiocarboxylate, an enolate or a mixture thereof, of a radionuclide selected from the group consisting of radioactive indium, radioactive gallium, lead-203, ruthenium-97, mercury-197 and thallium(III)-201, and (3), if desired, directions for use with a prescription for reacting (1) with (2).
Claim 12
Dependent Claim
108 words
A kit for performing a radiodiagnostic examination comprising (1) a protein which is provided with chelating groups derived from Desferrioxamine, 8-hydroxyquinoline, iminotriacetic acid-containing chelating agents, or iminodiacetic acid-containing chelating agents such as ethylenediamine tetracetic acid, diethylenetriamine pentacetic acid or diaminocyclohexyl tetracetic acid, or salts hereof, or a chelating peptide or polypeptide such as transferring,whether or not in the dry,state, (2) a solution of an oxinate, a carboxylate, a dithiocarboxylate, an enolate or a mixture thereof, of a radionuclide selected from the group consisting of radioactive indium, radioactive gallium, lead-203, ruthenium-97, mercury-197 and thallium(III)-201, and (3), if desired, directions for use with a prescription for reacting (1) with (2).
Claim 13
Dependent Claim
77 words
A kit as claimed in Claim 10,. comprising (1) a protein which is provided with chelating groups derived from diethylenetriamine pentacetic acid, or salts hereof, whether or not in the dry state, (2) a solution of a complex of a radionuclide selected from the group consisting of indium-111, gallium-67, lead-203 and ruthenium-97 with 8-hydroxyquinoline, acetyl acetone, citric acid, or a derivative hereof, and (3), if desired, directions for use with a prescription for reacting (1) with (2).
References Cited (Backward Citations)
USPTO Annuity & Maintenance Windows
Maintenance schedule is calculated for granted US utility patents.