Radioimmunoimaging with recombinant light chain of human monoclonal anti-lung cancer antibody HB4C in vivo study by using lung cancer xenografted mice

人抗肺癌单克隆抗体HB4C重组轻链放射免疫显像肺癌异种移植小鼠体内研究

• 批准号: 08671056
• 负责人: KUSAKABE Kiyoko
• 金额: $ 1.41万
• 依托单位: Tokyo Women's Medical College
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08671056/
• 关键词: Radioimmunodetection; Radioimmunotherapy; human monoclonal anti-lung cancer antibody; dHB4C5; 放射免疫検出法; 放射免疫治療法; ヒトモノクローナル抗体

The deglycosylated human monoclonal anti-lung cancer antibody, dHB4C5, has been establoshed it's specific recognition of lung cancer in vivo study. This dHB4C5 was labelled with In-DTPA which is adequate agent for imaging. Though higher accumulation of In-DTPA labeled dHB4C5 in the implanted tumor of mice than that's of In labeled control IgM was recognized, the remarkable uptake in liver, kidney, and spleen was also observed on images. The low affinity of In-DTPA to IgM,M900,0000 of dHB4C5, was thought to be limited application for clinical use because of high uptake in normal organs. Then, we tried to make recombinant light chain of dHB4C5, C5-L chain (C5lambda chain), and label with In-DTPA.The immunoactivity of C5lambda chain, however, was decreased compared with original C5lambda chain by using chelate DTPA.Furthermore, C5lambda chain labeled with In-111 DTPA was also accumulated in normal organs. On the otherhand, radioactive techinetium (Tc-99M), 6 hours physical half life, which is mostly used clinicaly, was applied to label with C5lambda chain. The accumulation of Tc-99m labeled C5lambda chain in tumor was shown on images 28 hours after administration clearly. Tc-99m labeled recombinant light chain C5lambda will become a promising imaging agent of lung cancer.

去糖基化的人抗肺癌单克隆抗体dHB4C5在体内研究中已经建立了对肺癌的特异性识别。该dHB4C5用In-DTPA标记，这是足够的成像剂。虽然发现in - dtpa标记的dHB4C5在小鼠植入肿瘤中的蓄积量高于in标记的对照IgM，但在图像上也观察到肝脏、肾脏和脾脏的显著摄取。in - dtpa对dHB4C5的IgM （m900000）的亲和力较低，由于在正常器官中摄取较高，因此被认为在临床应用中受到限制。然后，我们尝试制作重组dHB4C5轻链，C5-L链（C5lambda链），并用In-DTPA标记。然而，与原C5lambda链相比，螯合DTPA的免疫活性降低。此外，in -111 DTPA标记的C5lambda链也在正常器官中积累。另一方面，采用临床常用的6小时物理半衰期的放射性锝（Tc-99M），用C5lambda链标记。给药28小时后，图像清晰显示Tc-99m标记的C5lambda链在肿瘤中的积累。Tc-99m标记的重组轻链C5lambda将成为一种有前景的肺癌显像剂。

项目成果

日下部 きよ子: "アイソトープ療法" 臨床と研究. 74. 1704-1708 (1997)

Kiyoko Kusakabe：“同位素疗法”临床与研究。74。1704-1708（1997）。

日下部 きよ子: "非密封RIによる内照射療法" 新医療. 3. 90-93 (1996)

Kiyoko Kusakabe：“使用未密封 RI 的内部放射治疗”《新医学》3. 90-93 (1996)。

日下部 きよ子: "消化管ホルモン産生腫瘍の画像診断" 内分泌・糖尿病科. 2. 458-465 (1996)

Kiyoko Kusakabe：“胃肠道激素产生肿瘤的影像诊断”内分泌和糖尿病系2. 458-465（1996）。

日下部 きよ子: "口腔領域における最新の核医学診断-基礎と臨床-" Dental Diamond. 22. 146-151 (1997)

Kiyoko Kusakabe：“口腔区域的最新核医学诊断 - 基础和临床”牙科钻石。 22. 146-151 (1997)

日下部きよ子: "アイソトープ療法" 臨床と研究. 74. 1704-1708 (1997)

Kiyoko Kusakabe：“同位素疗法”临床与研究。74。1704-1708（1997）。