| Budget Amount *help |
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1992: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1991: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Research Abstract |
1.Animal studies of radiolabeled monoclonal antibodies. Technetium (Tc)-99m is an ideal radionuclide for clinical use. In the present research project, we developed a Tc-99m labeling method of monoclonal antibodies and compared with currently used radioiodinated or indium (In)-111 labeled antibodies. Tc-99m labeling of monoclonal antibodies were easily accomplished by mixing reduced antibodies with HMDP-kit for bone scintigraphy and Tc-99m pertechnetate. Specific activity was as high as 40 to 80 mCi/mg and labeling efficiency was more than 95%. Immunoreactivity of Tc-99m labeled antibodies was preserved as radioiodinated or In-111 labeled ones. Biodistribution studies using nude mice carrying human cancer demonstrated that tumor-to-normal orgran rations and tumor-to-blood ratios of Tc-99m labeled antibodies were higher than radioiodinated or In-111 labeled ones. Thus, Tc-99m labeled monoclonal antibodies seemed promising for imaging of cancer, myocardial infarction, infection and embol
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i. Furthe more, rhenium (Re)-186, which has excellent physisial properties for radiotherapy, is expected to show similar biodistribution with Tc-99m.
2. Clinical studies using Tc-99m labeled monoclonal antibodies. Monoclonal antibody BW431/26 reacts with CEA and Tc-99m labeled BW431/26 localizes well in transplanted human colorectal cancer tissues in nude mice. In the present research project, we performed immunoscintigraphy of colorectal cancer using Tc- 99m labeled BW431/26. At 19 to 24 hours after intravenous injection, 13 of 14 (92.8%) primary tumors were positively detected and 1 of2 (50%) cases with liver metastasis showed deposit of antibodies in the metastatic sites. Tumor-to-normal tissue rations of surgical obtained tissues were closely correlated with those presurgically obtained by single photon emission CT(SPECT),reaching to tumor-to-normal tissue ratio of 14.7. These results suggest that 1) Immunoscintigraphy using Tc-99m labeled monoclonal antibodies to CEA is useful for the localization of colorectal cancer, 2) Biodistribution and tumor uptake of Tc-99m labeled antibodies are presurgically estimated with SPECT. 3) Radiolabeled monoclonal antibodies will be applied to the radiotherapy of radiosensitive tumors, such as malignant lymphoma and small cell lung cancer, due to lhigh tumor-to-nomal tissue ratios. Less
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