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Pharmacokinetic Study of Targeting Tumors with Radio-and Drug-conjugated Monoclonal Antibody

放射性和药物结合的单克隆抗体靶向肿瘤的药代动力学研究

基本信息

批准号：
05670785
负责人：
NAKAMURA Kayoko
金额：
$ 1.34万
依托单位：
Keio University School of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1993
资助国家：
日本
起止时间：
1993 至 1994
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05670785/
关键词：
Radiolabeled Antibody Interferon Interleukin-2 Targeting Tumor De-ionization 癌

项目摘要

Using athymic mice bearing human tumor xenografts, the effects of several drugs on the pharmacokinetics and biodistribution of radiolabeled monoclonal antibody were investigated. The following results were obtained :(1)The administration of Interferon-minipellet which consisted of collagen and natural interferon-alpha could keep the blood interferon level constant for 5 days. It also enhanced the uptake of radiolabeled anti-CEA monoclonal antibody in tumors with twice comparing with control mice. It increased in the clearance of In-111 from blood, thus making the dosimetry of Y-99m-labeled antibody favorable for radioimmunotherapy.(2)The administration of IL-2 with low dose increased the uptake of Tc-99m-labeled antibody not in the tumor but also in some normal tissues. IL-2 could be conjugated with antibody without loss of its action which increases in the permeability of blood vessels. The biodistribution study of radiolabeled antibody conjugated with IL-2 is currently underway.(3)The administration of verapamil, lidocaine, monensin, or chloroquine could make tumor retention time of I-125-labeled antibody longer. They increased the blood clearance rate of I-125, thus increasing the tumor-to-blood ratio remarkably.These experimental results indicated that drugs investigated augment the efficacy of targeting of tumors with iodine-labeled antibody.

以人肿瘤移植胸腺小鼠为实验对象，研究了几种药物对单克隆抗体药代动力学和生物分布的影响。结果表明：(1)由胶原蛋白和天然干扰素- α组成的干扰素微球可使血清干扰素水平维持5 d不变。与对照小鼠相比，它还增加了肿瘤中放射性标记抗cea单克隆抗体的摄取，增加了两倍。它增加了血液中in -111的清除率，从而使y -99m标记抗体的剂量测定有利于放射免疫治疗。(2)低剂量IL-2不仅在肿瘤中增加了tc -99m标记抗体的摄取，而且在一些正常组织中也增加了tc -99m标记抗体的摄取。IL-2可以与抗体结合而不丧失其作用，从而增加血管的通透性。放射性标记抗体与IL-2偶联的生物分布研究正在进行中。(3)维拉帕米、利多卡因、莫能菌素或氯喹可延长i -125标记抗体的肿瘤滞留时间。他们提高了I-125的血液清除率，从而显著提高了肿瘤与血液的比率。这些实验结果表明，所研究的药物增强了碘标记抗体靶向肿瘤的功效。