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Optimization of radioimmunotherapy with radiolabeled anti-HER2 antibody

放射性标记抗 HER2 抗体放射免疫治疗的优化

基本信息

批准号：
15591299
负责人：
HOSONO Makoto
金额：
$ 1.98万
依托单位：
Kinki University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2006
项目状态：
已结题

项目摘要

Molecular targeting concept and technology have recently been established and applied to disease entities, and have proved efficient and indispensable in some pathological status. As one of molecular targeting applications, radioimmunoscintigraphy and radioimmunotherapy which use radiolabeled monoclonal antibodies recognizing malignancy have successfully been undertaken in laboratory studies and clinical applications. The purpose of this study was to develop tumor imaging and therapy using molecular targeting techniques. To conduct radioimmunotherapy with radiolabeled anti-HER2 antibody in patients, we investigated conditions of radiolabeling techniques of potentially therapeutic radionuclides and tumor-directed antibodies. Chelating agents having macrocycle structures are suitable for radioimmunotherapy because of conjugation stability. Parameters of radiolabeling for chelates have been determined and optimized in animal models with human cancers. Distributions of malignant cells were studied in animal models using radiolabeling of cancer cells. A liver metastasis model was constructed by injecting radiolabeled cancer cells into the portal vein or spleen. Biodistribution of cancer cells was determined by tracer studies using radiolabeled antibodies. The obtained data were used for analyzing parameters in forthcoming radioimmunotherapy. Basic safety standards in radiological protection were considered for prospects of radionuclide therapy in clinical facilities. In conclusion, our study demonstrates significant findings of basic investigation as molecular imaging and therapy are increasingly applied to clinical practices.

分子靶向的概念和技术是近年来发展起来的，并已应用于疾病实体，在某些病理状态下被证明是有效和不可或缺的。放射免疫显像和放射免疫治疗作为分子靶向治疗的一种应用，利用放射性标记的抗肿瘤单克隆抗体进行放射免疫显像和放射免疫治疗，已在实验室研究和临床应用中获得成功。本研究的目的是利用分子靶向技术发展肿瘤成像和治疗。为了在患者中使用放射性标记的抗HER2抗体进行放射免疫治疗，我们研究了潜在治疗性放射性核素和肿瘤导向抗体的放射性标记技术的条件。具有大环结构的螯合剂由于缀合稳定性而适用于放射免疫疗法。螯合物的放射性标记参数已在人类癌症动物模型中确定和优化。使用癌细胞的放射性标记在动物模型中研究恶性细胞的分布。通过将放射性标记的癌细胞注射到门静脉或脾脏中来构建肝转移模型。癌细胞的生物分布通过使用放射性标记抗体的示踪剂研究来确定。所获得的数据被用于分析即将到来的放射免疫治疗的参数。放射防护的基本安全标准被认为是放射性核素治疗在临床设施的前景。总之，我们的研究表明，随着分子成像和治疗越来越多地应用于临床实践，基础研究的重要发现。