| Project/Area Number |
61570509
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Radiation science
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| Research Institution | Kyoto University |
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Principal Investigator |
ENDO Keigo Department of Nuclear Medicine, Faculty of Medicine Kyoto University, 医学部, 助教授 (10115800)
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| Co-Investigator(Kenkyū-buntansha) |
KONISHI Junji Department of Nuclear Medicine, Fuculty of Medicine Kyoto University, 医学部, 教授 (70026970)
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| Project Period (FY) |
1986 – 1987
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| Project Status |
Completed (Fiscal Year 1987)
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| Budget Amount *help |
¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1987: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1986: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Keywords | monoclonal antibody / radioimmunoimaging / radioimmunotherapy / Indium-111 / 悪性黒色腫 / ガリウムー67 / インディウム-111 / 骨肉腫 / ヌードマウス |
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| Research Abstract |
Recently, monoclonal antibodies that recognize tumor-associated antigen are used to carry drugs, toxins, or radionuclides to cancer tissues. Success in radioimmunoimaging of tumors depends on the selection of monoclonal antibodies and radionuclides. In order to choose optimum antibodies for in vivo use, the relationship between in vitro cell binding and in vivo tumor accumulation of three radiolabeled antibodies was studied using I-125 and In-111 labeled monoclonal antibodies to human osteosarcoma, and human osteosarcoma xenograft in nude mice. In vitro binding studies can be used to exclude from in vivo use those antibodies which show very poor binding in vitro.
To assess the in vivo behavior of cytotoxic agents linked to antibodies, deferoxamine, known to form stable chelates with Ga-67, was conjugated with monoclonal antibodies using three different methods. Antibodies were efficiently labeled with Ga-67 through chelation with deferoxamine without losing antigen-binding capability. G
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a-67 labeled antibodies clearly visualized transplanted tumors in nude mice. However, the biodistribution of radioactivity was markedly different with the coupling methods used for the conjugation if deferoxamine and antibodies. Antibody conjugates linked by thioether bonds are a better choice for drug targeting and that Ga-67 labeled antitumor monoclonal antibodies are useful not noly for the immunoscintigraphy but also for the quantitative assessment and Visualization of the biodistribution of drug-antibody conjugates.
Immunoscintigraphy and pharmacokinetics of In-111 labeled ZME-018 monoclonal antibody were performed on 8 patients with malignant melanoma. Each patient received a single intravenous infusion of 20 mg ZME-018, coupled to 3 mCi In-111 without any acute toxicity. immunoscintigraphy of In-111 labeled ZME-018 antibody is safe and useful for the dectection of metastatic lesions in a selected group of patients with malignant melanoma. Further clinical evaluation of immunoscintigraphy is warranted. Less
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