Tumor localization and therapy with labeled antibodies specific to intracellular tumor-associated markers
First Claim
1. A method for detecting and localizing a tumor which either produces or is associated with an intracellular marker substance, which comprises injecting a human subject parenterally with an antibody specific to said marker substance and radiolabeled with a pharmacologically inert radioisotope capable of detection using a photoscanning device, and normal immunoglobulin from the same or different species as that used to prepare said specific antibody, said normal immunoglobulin being radio-labeled with a different isotope of the same element used to label the specific antibody, said different isotope emitting at a different energy from the marker-specific antibody label and being capable of independent detection by said photoscanning device;
- and subsequently scanning with said device, the level of activity of said normal immunoglobulin being used to determine the background activity due to non-targeted specific antibody, said background activity being subtracted from the total activity of the specific antibody, whereby the activity of substantially only the targeted, tumor-associated antibody is determined, and thereby detecting and localizing the site or sites of uptake of said labeled antibody by said tumor.
1 Assignment
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Accused Products
Abstract
Methods are provided for using radiolabeled antibodies specific to intracellular tumor-associated markers for detection, locatization and therapy of tumors. Antibodies and injectable compositions for use in the methods of the invention are also provided.
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Citations
26 Claims
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1. A method for detecting and localizing a tumor which either produces or is associated with an intracellular marker substance, which comprises injecting a human subject parenterally with an antibody specific to said marker substance and radiolabeled with a pharmacologically inert radioisotope capable of detection using a photoscanning device, and normal immunoglobulin from the same or different species as that used to prepare said specific antibody, said normal immunoglobulin being radio-labeled with a different isotope of the same element used to label the specific antibody, said different isotope emitting at a different energy from the marker-specific antibody label and being capable of independent detection by said photoscanning device;
- and subsequently scanning with said device, the level of activity of said normal immunoglobulin being used to determine the background activity due to non-targeted specific antibody, said background activity being subtracted from the total activity of the specific antibody, whereby the activity of substantially only the targeted, tumor-associated antibody is determined, and thereby detecting and localizing the site or sites of uptake of said labeled antibody by said tumor.
- View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15)
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16. An injectable composition, which comprises
(a) a substantially monospecific antibody having a specific immunoreactivity of at least 70% to an intracellular marker substance produced by or associated with a tumor and a cross-reactivity to non-tumor associated antigens of less than 15%; - said antibody being radiolabeled with one of Iodine-131 and Iodine-123 by direct substitution of iodine for hydrogen on the antibody molecule to an extent sufficient to reduce its specific immunoreactivity by from 5 to 33%;
(b) normal immunoglobulin from the same or different species as that used to prepare said specific antibody, said normal immunoglobulin being radiolabeled with the other of Iodine-131 and Iodine-123 by direct substitution of iodine for hydrogen on the immunoglobulin molecule; and (c) a pharmaceutically acceptable injection vehicle. - View Dependent Claims (17, 18, 19, 20)
- said antibody being radiolabeled with one of Iodine-131 and Iodine-123 by direct substitution of iodine for hydrogen on the antibody molecule to an extent sufficient to reduce its specific immunoreactivity by from 5 to 33%;
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21. An antibody which is specific to an intracellular marker substance produced by or associated with a tumor, said antibody being radiolabeled with a pharmacologically inert radioisotope capable of detection with a photoscanning device, said labeled antibody further containing in chemical combination at least one addend containing at least five atoms of boron with at least a natural abundance of Boron-10 isotope.
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22. An injectable composition, which comprises
(a) an antibody which is specific to an intracellular marker substance produced by or associated with a tumor, said antibody being radio-labeled with a pharmacologically inert radioisotope capable of detection with a photoscanning device, said labeled antibody further containing in chemical combination at least one addend containing at least five atoms of boron with at least a natural abundance of Boron-10 isotope; - and
(b) a pharmaceutically acceptable injection vehicle. - View Dependent Claims (23)
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- 24. A method of tumor radiotherapy, which comprises parenterally injecting into a human subject having a tumor which produces or is associated with an intracellular marker substance an effective tumor reducing amount of an antibody which is specific to said marker substance and radiolabeled with a pharmacologically inert, radiotherapeutically effective radioisotope.
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26. A method of tumor radiotherapy, which comprises parenterally injecting into a human subject having a tumor which produces or is associated with an intracellular marker substance a radiotherapeutically effective amount of an antibody which is specific to said marker substance and radiolabeled with a pharmacologically inert radioisotope capable of detection with a photo-scanning device, said labeled antibody further containing in chemical combination at least one addend containing at least five atoms of boron with at least a natural abundance of Boron-10 isotope;
- wherein the location of said tumor is determined using said photoscanning device, and a beam of thermal neutrons is then directed at said tumor location.
Specification