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Development of new diagnostic imaging and therapy using radiolabeled monoclonal antibodies (^<99m>Tc, ^<186>Re)

使用放射性标记单克隆抗体开发新的诊断成像和疗法（^<99m>Tc、^<186>Re）

基本信息

批准号：
07457195
负责人：
ENDO Keigo
金额：
$ 4.03万
依托单位：
Gunma University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1995
资助国家：
日本
起止时间：
1995 至 1996
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07457195/
关键词：
monoclonal antibody genetic engineering humanized antibody rhenium-186 レニムウ-186 テクネシウム-99m

项目摘要

Monoclonal antibodies are expected to carry radionuclides or drugs to the specific sites, and may be used for the imaging and/or therapy of cancer, infection, myocardial infarction, thrombus and others. However monoclonal antidoeies are derived of mice and cause anti-murine autibodies in patients who received murine-monoclonal antibodies. Humanized antibodies were constructed by genetically combined with small parts of antigen-binding sites of murine antibody and the human immunoglobulin.Two monoclonal antibodies, reactive with human ovarian cancer or human white blood cells were humanized by using the genetic engineering. Technetium-99m is an ideal radionuclide for imaging and was successfully labeled with humanized antibody. Obtained Tc-99m labeled antibody was stable in vivo and was clinically used under the guidance of the ethical committee of our institute.Humanized antibody was safely administered to ovarian cancer patients and localized in the ovarian cancer specimens. Tc-99m labeled humanized antibody to human leucocytes was also safely administered and clearly visualized normal bone marrow.Rehnium-186 emitts gamma-and beta-rays and is thought to be very effective for the therapy of cancers. The specific activity of Re-186 was too low to radiolabel antibodies. However, its binding to diphosphonates was stable and would be useful for the palliative therapy of bone pain caused by the metastasis of cancer.

单克隆抗体有望携带放射性核素或药物到达特定部位，并可用于癌症、感染、心肌梗死、血栓等的成像和/或治疗。然而，单克隆抗体来源于小鼠，在接受小鼠单克隆抗体的患者中引起抗小鼠抗体。人源化抗体是通过与小鼠抗体抗原结合位点和人免疫球蛋白的小片段基因结合构建的。利用基因工程技术将两种与人卵巢癌或人白细胞反应的单克隆抗体人源化。锝-99m是一种理想的成像放射性核素，已成功地用人源化抗体标记。获得的Tc-99m标记抗体在体内稳定，在我院伦理委员会指导下临床使用。人源化抗体可安全地用于卵巢癌患者，并可在卵巢癌标本中定位。Tc-99m标记的人白细胞人源抗体也被安全给予，并清晰可见正常骨髓。铼-186释放出伽马射线和β射线，被认为对治疗癌症非常有效。Re-186的特异性活性太低，无法对抗体进行放射性标记。然而，它与二膦酸盐的结合是稳定的，将有助于缓解癌症转移引起的骨痛。