Chimeric monoclonal antibody A7-Fab coupled to magnetic particles as a contrast agent of MR imaging

嵌合单克隆抗体 A7-Fab 与磁性颗粒偶联作为 MR 成像造影剂

• 批准号: 11671265
• 负责人: OTSUJI Eigo
• 金额: $ 2.24万
• 依托单位: Kyoto Prefectural University of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11671265/
• 关键词: monoclonal antibody; pancreatic cancer; MRI; contrast agent; A7; キメラ化抗体

The use of magnetic particles as contrast agents in MR imaging have been proposed. The total magnetic moment of ferromagnetic particles is approximately one order of magnitude larger than that found for paramagnetic materials of similar size. We coupled chimeric monoclonal antibody A7, which specifically reacts with human pancreatic carcinoma, to Lignosite FML (ferromagnetic particles) in order to improve the distinguishment between pancreatic carcinoma and other tissues. We examined the retaining in vitro immunoreactivity of ferromagnetic particles bound to ChA7Fab and their in vivo distribution in nude mice bearing human pancreatic carcinoma xenografts were examined. ChA7Fab-Lignosite FML retained binding activities nearly identical to ChA7Fab. Significantly more of the radiolabeled ChA7Fab-Lignosite FML accumulated in the tumor than did normal mouse IgGFab-Lignosite FML (P<0.05). ChA7Fab-Lignosite FML and ^<125>I labeled normal mouse IgGfab-Lignosite FML disappeared from blood rapidly. As for all resected normal tissues, the accumulation levels of ^<125>I labeled ChA7Fab-Lignosite FML were lower than those for the tumors and decreased linearly with time. From these experiments, we conclude that ChA7Fab coupled to Lignosite FML is suitable for contrast agent of MR imaging of human pancreatic carcinoma.

已经提出了在MR成像中使用磁性颗粒作为造影剂。铁磁颗粒的总磁矩比类似尺寸的顺磁材料的总磁矩大约大一个数量级。我们将与人胰腺癌特异性反应的嵌合单克隆抗体A7偶联到铁磁性颗粒（铁磁性颗粒）上，以改善胰腺癌与其他组织之间的结合。我们研究了保留在体外的免疫反应性结合ChA 7 Fab铁磁颗粒和它们在荷人胰腺癌异种移植物的裸鼠体内分布进行了检查。ChA 7 Fab-LPL位点FML保留了与ChA 7 Fab几乎相同的结合活性。放射性标记的ChA 7 Fab-Lactobacillus位点FML在肿瘤中的聚集量显著高于正常小鼠IgGFab-Lactobacillus位点FML（P<0.05）。ChA 7 Fab-Lactobacillus site FML和~<125>（13）I标记的正常小鼠IgGfab-Lactobacillus site FML从血液中迅速消失。对于所有切除的正常组织，^<125>I标记的ChA 7 Fab-Lignosite FML的积累水平低于肿瘤组织，并随时间线性下降。结果表明，ChA 7 Fab与Leptin位点FML偶联后，可作为胰腺癌MR成像的对比剂。

项目成果

E.Otsuji, A.Toma, S.Kobayashi, H.Cho, K.Okamoto, A.Hagiwara, H.Yamagichi.: "Long-term Benefit of Extended Lymphadenectomy With Gastrectomy in Distally Located Early Gastric Carcinoma."American Journal of Surgery. 180. 127-132 (2000)

E.Otsuji、A.Toma、S.Kobayashi、H.Cho、K.Okamoto、A.Hagiwara、H.Yamagichi.：“扩大淋巴结切除术联合胃切除术治疗远端早期胃癌的长期益处。”美国杂志

Eigo Otsuji,et al: "Total Gastrectomy with Simultaneous Poncreatico-Splenectomy or Splenectomy in Patients with advanced gastric Cancer"British Journal of Cancer. 79. 1789-1793 (1999)

Eigo Otsuji 等人：“晚期胃癌患者的全胃切除术同时胰脾切除术或脾切除术”英国癌症杂志。

"Application of 99mTc-labeled chimeric Fab fragments of monoclonal antibody A7 for radioimmunoscintigraphy of pancreatic cancer"108. 689-697 (1999)

“99mTc标记的单克隆抗体A7嵌合Fab片段在胰腺癌放射免疫闪烁显像中的应用”108。

E.Otsuji 他: "Outcome of prophylactic radical lymphadenectomy with gastectomy in patients with early gastric carcinoma lymphonde metestrum"Cancer. 89. 1425-1430 (2000)

E. Otsuji 等人：“早期胃癌淋巴结中段患者预防性根治性淋巴结切除术与胃切除术的结果”癌症。

E.Otsuji, T.A.Toma, S.Kobayashi, K.Okamoto, A.Hagiwara, H.Yamagishi.: "Outcome of prophylactic radical lymphadenectomy with gastrectomy in patients with early gastric carcinoma without lymph node metastasis."Cancer. 89. 1425-1430 (2000)

E.Otsuji、T.A.Toma、S.Kobayashi、K.Okamoto、A.Hagiwara、H.Yamagishi.：“预防性根治性淋巴结切除术联合胃切除术治疗无淋巴结转移的早期胃癌患者的结果。”癌症。