CA2133833A1 - Method and kit for imaging and treating organs and tissues - Google Patents

Method and kit for imaging and treating organs and tissues

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Publication number
CA2133833A1
CA2133833A1 CA002133833A CA2133833A CA2133833A1 CA 2133833 A1 CA2133833 A1 CA 2133833A1 CA 002133833 A CA002133833 A CA 002133833A CA 2133833 A CA2133833 A CA 2133833A CA 2133833 A1 CA2133833 A1 CA 2133833A1
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antibody
agent
fragment
organ
composition
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CA2133833C (en
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Milton D. Goldenberg
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Immunomedics Inc
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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01R—MEASURING ELECTRIC VARIABLES; MEASURING MAGNETIC VARIABLES
    • G01R33/00—Arrangements or instruments for measuring magnetic variables
    • G01R33/20—Arrangements or instruments for measuring magnetic variables involving magnetic resonance
    • G01R33/44—Arrangements or instruments for measuring magnetic variables involving magnetic resonance using nuclear magnetic resonance [NMR]
    • G01R33/48—NMR imaging systems
    • G01R33/54—Signal processing systems, e.g. using pulse sequences ; Generation or control of pulse sequences; Operator console
    • G01R33/56—Image enhancement or correction, e.g. subtraction or averaging techniques, e.g. improvement of signal-to-noise ratio and resolution
    • G01R33/5601—Image enhancement or correction, e.g. subtraction or averaging techniques, e.g. improvement of signal-to-noise ratio and resolution involving use of a contrast agent for contrast manipulation, e.g. a paramagnetic, super-paramagnetic, ferromagnetic or hyperpolarised contrast agent
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K49/00—Preparations for testing in vivo
    • A61K49/06—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations
    • A61K49/08—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by the carrier
    • A61K49/10—Organic compounds
    • A61K49/14—Peptides, e.g. proteins
    • A61K49/16—Antibodies; Immunoglobulins; Fragments thereof
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    • A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
    • A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
    • A61K51/04—Organic compounds
    • A61K51/08—Peptides, e.g. proteins, carriers being peptides, polyamino acids, proteins
    • A61K51/10—Antibodies or immunoglobulins; Fragments thereof, the carrier being an antibody, an immunoglobulin or a fragment thereof, e.g. a camelised human single domain antibody or the Fc fragment of an antibody
    • A—HUMAN NECESSITIES
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    • A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
    • A61K51/04—Organic compounds
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    • A61K51/10—Antibodies or immunoglobulins; Fragments thereof, the carrier being an antibody, an immunoglobulin or a fragment thereof, e.g. a camelised human single domain antibody or the Fc fragment of an antibody
    • A61K51/1018—Antibodies or immunoglobulins; Fragments thereof, the carrier being an antibody, an immunoglobulin or a fragment thereof, e.g. a camelised human single domain antibody or the Fc fragment of an antibody against material from animals or humans
    • A—HUMAN NECESSITIES
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    • A61K51/1027—Antibodies or immunoglobulins; Fragments thereof, the carrier being an antibody, an immunoglobulin or a fragment thereof, e.g. a camelised human single domain antibody or the Fc fragment of an antibody against receptors, cell-surface antigens or cell-surface determinants
    • A61K51/1036—Antibodies or immunoglobulins; Fragments thereof, the carrier being an antibody, an immunoglobulin or a fragment thereof, e.g. a camelised human single domain antibody or the Fc fragment of an antibody against receptors, cell-surface antigens or cell-surface determinants against hormone receptors
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    • A61K51/1027—Antibodies or immunoglobulins; Fragments thereof, the carrier being an antibody, an immunoglobulin or a fragment thereof, e.g. a camelised human single domain antibody or the Fc fragment of an antibody against receptors, cell-surface antigens or cell-surface determinants
    • A61K51/1039—Antibodies or immunoglobulins; Fragments thereof, the carrier being an antibody, an immunoglobulin or a fragment thereof, e.g. a camelised human single domain antibody or the Fc fragment of an antibody against receptors, cell-surface antigens or cell-surface determinants against T-cell receptors
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61K51/04—Organic compounds
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    • A61K51/1045—Antibodies or immunoglobulins; Fragments thereof, the carrier being an antibody, an immunoglobulin or a fragment thereof, e.g. a camelised human single domain antibody or the Fc fragment of an antibody against animal or human tumor cells or tumor cell determinants
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    • A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
    • A61K51/04—Organic compounds
    • A61K51/08—Peptides, e.g. proteins, carriers being peptides, polyamino acids, proteins
    • A61K51/10—Antibodies or immunoglobulins; Fragments thereof, the carrier being an antibody, an immunoglobulin or a fragment thereof, e.g. a camelised human single domain antibody or the Fc fragment of an antibody
    • A61K51/1045—Antibodies or immunoglobulins; Fragments thereof, the carrier being an antibody, an immunoglobulin or a fragment thereof, e.g. a camelised human single domain antibody or the Fc fragment of an antibody against animal or human tumor cells or tumor cell determinants
    • A61K51/1057—Antibodies or immunoglobulins; Fragments thereof, the carrier being an antibody, an immunoglobulin or a fragment thereof, e.g. a camelised human single domain antibody or the Fc fragment of an antibody against animal or human tumor cells or tumor cell determinants the tumor cell being from liver or pancreas
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
    • A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
    • A61K51/04—Organic compounds
    • A61K51/08—Peptides, e.g. proteins, carriers being peptides, polyamino acids, proteins
    • A61K51/10—Antibodies or immunoglobulins; Fragments thereof, the carrier being an antibody, an immunoglobulin or a fragment thereof, e.g. a camelised human single domain antibody or the Fc fragment of an antibody
    • A61K51/1045—Antibodies or immunoglobulins; Fragments thereof, the carrier being an antibody, an immunoglobulin or a fragment thereof, e.g. a camelised human single domain antibody or the Fc fragment of an antibody against animal or human tumor cells or tumor cell determinants
    • A61K51/1072—Antibodies or immunoglobulins; Fragments thereof, the carrier being an antibody, an immunoglobulin or a fragment thereof, e.g. a camelised human single domain antibody or the Fc fragment of an antibody against animal or human tumor cells or tumor cell determinants the tumor cell being from the reproductive system, e.g. ovaria, uterus, testes or prostate
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B82—NANOTECHNOLOGY
    • B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
    • B82Y5/00—Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2123/00—Preparations for testing in vivo
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10S424/00—Drug, bio-affecting and body treating compositions
    • Y10S424/81—Drug, bio-affecting and body treating compositions involving autoimmunity, allergy, immediate hypersensitivity, delayed hypersensitivity, immunosuppression, immunotolerance, or anergy
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10S530/00—Chemistry: natural resins or derivatives; peptides or proteins; lignins or reaction products thereof
    • Y10S530/868—Chemistry: natural resins or derivatives; peptides or proteins; lignins or reaction products thereof involving autoimmunity, allergy, immediate hypersensitivity, delayed hypersensitivity, immunosuppression, or immunotolerance

Abstract

2133833 9319668 PCTABS00027 Provided are methods and compositions for detecting and treating normal, hypoplastic, ectopic or remnant tissue, organ or cells in a mammal. The method comprises parenterally injecting a mammalian subject, at a locus and by a route providing access to said tissue or organ, with a composition comprising antibody/fragment which specifically binds to targeted organ, tissue or cell. The antibody/fragment may be administered alone, or labeled or conjugated with an imaging, therapeutic, cytoprotective or activating agent.

Claims (57)

1. A method of imaging hypoplastic, anatomically displaced or ectopic cells or tissues in a mammalian subject by scintigraphic or magnetic resonance imaging, comprising the steps of: (a) parenterally injecting a mammalian subject, at a locus and by a route providing access to an organ of interest, with an antibody or antibody fragment which specifically binds a marker produced by or associated with said cell or tissue, said antibody or antibody fragment being labeled with a radioisotope or with a magnetic resonance image enhancing agent capable of external detection, the amount of the labeled antibody or antibody fragment being sufficient to permit a scintigraphic image or an enhanced magnetic resonance image of said organ to be obtained; and (b) obtaining a positive scintigraphic image or positive enhanced magnetic resonance image of said organ, at a time after injection of said agent sufficient for the imaging principle to diffusely accrete in said organ and specifically bind to said marker.
2. A method for detecting organ tissue retained after surgical removal of a portion of the organ, wherein the organ tissue produces or is associated with a marker substance, the method comprising injecting a human subject parenterally with an antibody specific to the marker substance and radiolabeled with a pharmacologically inert radioisotope or magnetic resonance imaging agent capable of detection using a photoscanning or magnetic resonance imaging device.
3. A method for determining in a mammal, a first organ's condition, the first organ producing or being associated with a marker substance and being adjacent to a second organ which has been surgically removed from the mammal; the method comprising injecting the mammal parenterally with an antibody specific to the marker substance and radiolabeled with a pharmacologically inert radioisotope or magnetic resonance imaging agent capable of detection using a photoscanning or magnetic resonance imaging agent device, wherein the condition of the first organ is determined.
4. The method of any one of claims 1, 2 or 3, wherein the cell, tissue or organ is pretargeted with a first composition comprising an avidin-conjugated antibody to be used in conjunction with biotin, biotinylated antibody to be used in conjunction with avidin, bifunctional antibody, antibody-hapten complexes, or enzyme-conjugated antibody, wherein the antibody is an antibody or antibody fragment which specifically binds a marker produced by or associated with said cell, tissue or organ, and after the first composition accretes at the targeted tissue, cell or organ, a second composition, which bears the imaging principle, is administered which activates the first composition or couples with the first composition to produce a desired effect.
5. The method of any one of claims 1, 2 or 3, wherein the isotope emits at 50- 1,500 kev energy.
6. The method of any one of claims 1, 2 or 3, wherein the mri enhancing agent is a species of Gadolinium, Iron, Manganese, Rhenium, Europium, Lanthanium, Holmium, or Terbium.
7. The method of claim 4, wherein the cell, tissue or organ is targeted by injecting the subject with the first composition which comprises biotinylated antibody or fragment, optionally injecting the patient with a clearing composition comprising an agent to clear circulating biotinylated antibody or fragment, injecting the subject with avidin, and then injecting the second composition which comprises biotin conjugated with isotope or mri enhancing agent.
8. The method of any one of claims 1, 2 or 3, wherein the antibody or fragment is a Fv, single chain antibody, Fab, Fab', (Fab)2 or F(ab')2 fragment or intact antibody.
9. The method of any one of claims 1, 2 or 3, wherein the antibody or fragment has a specific immunoreactivity to targeted cells or tissues of at least 60% and a cross-reactivity to other antigens of less than 35%.
10. A method for treating hypoplastic or ectopic tissue which produces or is associated with a marker substance, which comprises injecting a human subject parenterally with an antibody specific to the marker substance and conjugated with a cytotoxic agent.
11. The method of claim 10, wherein the tissue is ectopic.
12. The method of claim 11, wherein the ectopic tissue is endometrium.
13. A method for ablating non-malignant cells or tissues in a patient, the method comprising treating the patient with an antibody or antibody fragment specific to a marker associated with or produced by the cell to be ablated and which is conjugated to a cytotoxic agent.
14. A method for destroying bone-marrow cells in a patient prior to regrafting with normal bone marrow cells, the method comprising treating the patient with an antibody or antibody fragment specific to a marker associated with or produced by bone marrow cells and which is conjugated to a cytotoxic agent.
15. The method of any of claims 10, 13 or 14, wherein the cell or tissue is pretargeted with a first composition comprising an avidin-conjugated antibody to be used in conjunction with biotin, biotinylated antibody used in conjunction with avidin, bifunctional antibody, antibody-hapten complexes, or enzyme-conjugated antibody, wherein the antibody is an antibody or antibody fragment which specifically binds to said marker, and after the first composition accretes at the targeted tissue or cell, a second composition is administered which activates a therapeutic agent on the first composition or couples a therapeutic agent to the first composition to produce a therapeutic effect.
16. The method of any of claims 10, 13 or 14, wherein the cytotoxic agent is an isotope, drug, toxin, fluorescent dye activated by nonionizing radiation, hormone, autocrine or cytokine.
17. The method of any of claims 10, 13 or 14, wherein the cell or tissue is pretargeted by injecting the subject with the first composition which comprises biotinylated antibody or fragment, optionally injecting the patient with a clearing composition comprising an agent to clear circulating biotinylated antibody or fragment, and then injecting the second composition which comprises biotin conjugated with the cytotoxic agent.
18. The method of any of claims 10, 13 or 14, wherein the antibody or fragment is a Fv, single chain antibody, Fab, Fab', or F(ab')2 fragment or intact antibody.
19. The method of any of claims 10, 13 or 14, wherein the antibody or fragment has a specific immunoreactivity to targeted cells or tissues of at least 60% and a cross-reactivity to other antigens of less than 35%.
20. The method of claim 16, wherein the cytotoxic agent is a radioisotope selected from the group consisting of Iodine-125, Iodine-131, Rhenium-186, Rhenium-188, Silver-111, Platinum-197, Palladium-109, Copper-67, Phosphorus-32, Phosphorus-33, Yttrium-90, Scandium-47, Samarium-153, Lutetium-177, Rhodium-105, Praseodymium-142, Praseodymium-143, Terbium-161, Holmium-166 and Gold-199.
21. The method of claim 16, wherein the cytotoxic agent is taxol, mechlorethamine, cyclophosphamide, melphalan, uracil mustard, chlorambucil, thiotepa, busulfan, carmustine, lomustine, semustine, streptozocin, dacarbazine, methotrexate, fluorouracil, cytarabine, azaribine, mercaptopurine, thioguanine, vinblastine, vincristine, dactinomycin, daunorubicin, doxorubicin, bleomycin, mithramycin, mitomycin, L-asparaginase, cisplatin, hydroxyurea, procarbazine, mitotane, prednisone, hydroxyprogesterone caproate, medroprogesterone acetate, diethylstilbestrol, ethinyl estradiol, tamoxifen, and testosterone propionate or fluoxymesterone.
22. A sterile injectable composition for human use, comprising an antibody or antibody fragment specific to an antigen associated with or produced by non-malignant cells or bone marrow cells, conjugated with a cytotoxic agent, in a pharmaceutically acceptable sterile injection vehicle.
23. A cytoprotective conjugate, comprising an antibody or antibody fragment specific to an antigen produced by or associated with cells of a normal organ or tissue, which is conjugated to a cytoprotective agent which protects the cells of said normal organ or tissue against the cytotoxic action of radiation or a cytotoxic drug or toxin.
24. The cytoprotective conjugate of claim 23, in the form of a sterile injectable composition for human use, comprising said conjugate dissolved or dispersed in a pharmaceutically acceptable sterile injection vehicle.
25. The cytoprotective conjugate of claim 23 or 24, wherein said antibody or fragment is a Fv, single chain antibody, Fab, Fab', or F(ab')2 fragment or intact antibody.
26. The cytoprotective conjugate of claim 23 or 24, wherein said cytoprotective agent is WR-2721 or WR-1065.
27. In a method of therapy of cancer, wherein a human patient suffering from a cancer susceptible to treatment with radiation or a cytotoxic agent is treated with a therapeutic amount of cytotoxic radiation or a cytotoxic drug or toxin, the improvement comprising administering to said patient a cytoprotective amount of the cytoprotective conjugate of any of claims 23-26.
28. The method of claim 27, wherein said cytotoxic radiation, drug or toxin is administered in the form of a tumor targeting antibody or fragment specific to an antigen produced by or associated with a cancer cell, the targeting antibody or fragment being conjugated to a radioisotope, drug or toxin.
29. The method of claim 27, wherein the cells of said normal organ or tissue are pretargeted with a first composition comprising an avidin-conjugated antibody to be used in conjunction with biotin, biotinylated antibody used in conjunction with avidin, bifunctional antibody, antibody-hapten complexes, or enzyme-conjugated antibody, wherein the antibody is an antibody or antibody fragment which specifically binds a marker produced by or associated with said cells, and after the first composition accretes at the targeted organ or tissue, a second composition is administered which couples said cytoprotective agent to the first composition to form said cytoprotective conjugate and produce the cytoprotective effect.
30. The method of claim 29, wherein the cells of said normal organ or tissue are pretargeted by injecting the subject with the first composition which comprises biotinylated antibody or fragment, optionally injecting the patient with a clearing composition comprising an agent to clear circulating biotinylated antibody or fragment, injecting the subject with avidin, and then injecting the second composition which comprises biotin conjugated with said cytoprotective agent.
31. A kit comprising, in suitable containers, (A) the cytoprotective conjugate of claim 23 or 24, and (B) a tumor targeting antibody or fragment specific to an antigen produced by or associated with a cancer cell, the targeting antibody or fragment being conjugated to a radioisotope, drug or toxin.
32. A method of affecting a function of a non-malignant cell in a mammalian subject, the method comprising administering to the subject a composition comprising an antibody specific to a growth factor receptor or hormone receptor on the targeted cell, wherein the antibody affects the function and proliferation of the cell.
33. A method of treating a condition affecting non-malignant cells in a mammalian subject, the method comprising administering to a subject requiring such treatment, a composition comprising an antibody or fragment specific to a hormone receptor or growth factor on a targeted cell, wherein the antibody or fragment is conjugated to a therapeutic agent.
34. A therapeutic conjugate comprising an antibody or fragment specific to a growth factor receptor or hormone receptor and a therapeutic agent.
35. The therapeutic conjugate of claim 34 wherein the therapeutic agent is an isotope, drug, toxin, hormone antagonist, cytokine, autocrine, or fluorescent dye activated by nonionizing radiation.
36. An immunological method of affecting a hormonal function of a cell in a mammalian subject, the method comprising administering to the subject a composition comprising an antibody or fragment specific to a hormone receptor on a targeted cell, wherein the antibody or fragment affects the hormonal function of the targeted cell.
37. The method of claim 36, wherein the antibody or fragment is conjugated to a therapeutic agent.
38. The method of claim 36, wherein the hormonal cell is of the ovary, breast, or testis.
39. The method of claim 3,8 wherein the receptor is an FSH receptor or an LH receptor.
40. The method of claim 39, wherein the affected hormonal function produces amenorrhea or sterility.
41. The method of claim 36, wherein the receptor is an FSH or estrogen receptor.
42. The method of claim 41, wherein the affect is to treat fibrocystic breast disease.
43. The method of claim 36, wherein the hormone-dependent cell is of the prostate.
44. The method of claim 43, wherein the receptor is an androgen receptor.
45. The method of claim 13, wherein said marker is a hormone receptor or growth factor receptor, and wherein said cytotoxic agent is a chemical or radiation ablation agent.
46. The method of claim 45, wherein the antibody to ovarian cell or receptor thereof is used to ablate or reduce the ovaries or its function.
47. The method of claim 45, wherein the antibody to prostate cells or receptor thereof is used to ablate or reduce the prostate or its functions.
48. Use of an antibody or antibody fragment which specifically binds a marker produced by or associated with a cell or tissue in an organ of interest, said antibody or antibody fragment being labeled with a radioisotope or with a magnetic resonance image enhancing moiety capable of external detection, to prepare an imaging agent for use in a method of imaging hypoplastic, anatomically displaced or ectopic cells or tissues in a mammalian subject by scintigraphic or magnetic resonance imaging, wherein: (a) a mammalian subject is parenterally injected, at a locus and by a route providing access to an organ of interest, with said imaging agent, the amount of the agent being sufficient to permit a scintigraphic image or an enhanced magnetic resonance image of said organ to be obtained; and (b) a positive scintigraphic image or positive enhanced magnetic resonance image of said organ is obtained, at a time after injection of said agent sufficient for the imaging principle to diffusely accrete in said organ and specifically bind to said marker.
49. Use of an antibody specific to a marker substance produced by or associated with an organ tissue, and radiolabeled with a pharmacologically inert radioisotope or magnetic resonance imaging moiety capable of detection using a photoscanning or magnetic resonance imaging device, to prepare an agent for use in a method for detecting organ tissue retained after surgical removal of a portion of the organ, wherein in the method, a human subject is injected parenterally with said agent, and residual organ tissue is detected.
50. Use of an antibody specific to a marker substance produced by or associated with a first organ, and radiolabeled with a pharmacologically inert radioisotope or magnetic resonance imaging moiety capable of detection using a photoscanning or magnetic resonance imaging device, to prepare an agent for use in a method for determining, in a mammal, a first organ's condition, said first organ being adjacent to a second organ which has been surgically removed from the mammal, wherein in the method, the mammal is injected parenterally with said agent, and the condition of said first organ is determined.
51. Use of an antibody specific to a marker substance produced by or associated with hypoplastic or ectopic tissue and conjugated with a cytotoxic agent, to prepare an agent for use in a method for treating hypoplastic or ectopic tissue, wherein in the method, a human subject burdened with such tissue and in need of treatment thereof is injected parenterally with said agent.
52. Use of an antibody or antibody fragment specific to a marker associated with or produced by non-malignant cells or tissues and conjugated to a cytotoxic agent, to prepare an agent for use in a method for ablating non-malignant cells or tissues in a patient, wherein in the method, a patient is treated with said agent.
53. Use of an antibody or antibody fragment specific to a marker associated with or produced by bone marrow cells and conjugated to a cytotoxic agent, to prepare an agent for use in a method for destroying bone-marrow cells in a patient prior to regrafting with normal bone marrow cells, wherein in the method, the patient is treated with said agent and said bone-marrow cells are destroyed.
54. Use of a cytoprotective conjugate, comprising an antibody or antibody fragment specific to an antigen produced by or associated with cells of a normal organ or tissue, which is conjugated to a cytoprotective agent which protects the cells of said normal organ or tissue against the cytotoxic action of radiation or a cytotoxic drug or toxin, to prepare an agent for use in a method of therapy of cancer, wherein in the method, a human patient suffering from a cancer susceptible to treatment with radiation or a cytotoxic agent is treated with a therapeutic amount of cytotoxic radiation or a cytotoxic drug or toxin, and wherein a cytoprotective amount of said cytoprotective conjugate is administered to said patient.
55. Use of an antibody specific to a growth factor receptor or hormone receptor on a targeted non-malignant cell in a mammalian subject, wherein said antibody affects the function and proliferation of said cell, to prepare an agent for use in a method of affecting a function of said cell, wherein in the method, the mammalian subject is treated with a composition comprising said agent.
56. Use of an antibody or fragment specific to a hormone receptor or growth factor on a targeted cell, wherein the antibody or fragment is conjugated to a therapeutic agent, to prepare an agent for use in a method of treating a condition affecting non-malignant cells in a mammalian subject, wherein in the method, a composition comprising said agent is administered to a subject requiring such treatment.
57. Use of an antibody or fragment specific to a hormone receptor on a targeted cell, wherein the antibody or fragment affects the hormonal function of the targeted cell, to prepare an agent for use in an immunological method of affecting a hormonal function of a cell in a mammalian subject, wherein in the method, a composition comprising said agent is administered to the subject.
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