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Diagnostic imaging using monoclonal antibodies (Development of Tc-99m and Re-186 labeling)

使用单克隆抗体的诊断成像（Tc-99m和Re-186标记的开发）

基本信息

批准号：
03670543
负责人：
ENDO Keigo
金额：
$ 1.28万
依托单位：
Gunma University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1991
资助国家：
日本
起止时间：
1991 至 1992
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-03670543/
关键词：
monoclonal antibodies technetium-99m rhenium-186 colorectal cancer CEA immunoscintigraphy レニウムー186 卵巣癌

项目摘要

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 … More 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

1.放射性标记单克隆抗体的动物研究。锝（Tc）-99m是一种理想的临床应用放射性核素。本研究建立了单克隆抗体的Tc-99 m标记方法，并与目前使用的放射性碘标记或铟（In）-111标记的抗体进行了比较。单克隆抗体的~（99）Tc标记可通过将还原抗体与骨显像用HMDP-kit和~（99）Tc-高锝酸盐混合而容易地完成。比活度高达40 ~ 80 mCi/mg，标记效率大于95%。Tc-99 m标记的抗体的免疫反应性与放射性碘标记或In-111标记的抗体相同。用荷人癌裸鼠进行的生物分布研究表明，Tc-99 m标记抗体的肿瘤/正常组织比和肿瘤/血液比均高于放射性碘标记抗体或In-111标记抗体。因此，Tc-99 m标记的单克隆抗体有望用于肿瘤、心肌梗塞、感染和栓塞的显像。 ...更多信息 I.此外，具有良好的放射治疗物理特性的Tc（Re）-186有望显示出与Tc-99 m相似的生物分布。使用Tc-99 m标记的单克隆抗体的临床研究。单克隆抗体BW 431/26可与CEA反应，99 mTc标记的BW 431/26在裸鼠移植的人大肠癌组织中定位良好。在本研究项目中，我们使用Tc-99 m标记的BW 431/26进行结直肠癌的免疫闪烁显像。静脉注射后19 ~ 24小时，14例原发灶中13例（92.8%）抗体阳性，2例肝转移灶中1例（50%）抗体存款于转移灶。手术获得的组织的肿瘤与正常组织的比值与术前通过单光子发射CT（SPECT）获得的组织的肿瘤与正常组织的比值密切相关，达到14.7。结果提示：（1）~（99）Tc-CEA单克隆抗体免疫闪烁显像对结直肠癌的定位是有用的;（2）~（99）Tc-CEA单克隆抗体的生物分布和肿瘤摄取是用SPECT进行预测的。3)放射性标记的单克隆抗体将被应用于放射敏感性肿瘤的放射治疗，如恶性淋巴瘤和小细胞肺癌，由于肿瘤与正常组织的比例高。少