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Studies on drug delivery and imaging for tumors by use of monoclonal antibodies against membrane enzymes

利用抗膜酶单克隆抗体进行肿瘤药物递送和成像研究

基本信息

批准号：
62570993
负责人：
HIRANO Kazuyuki
金额：
$ 1.34万
依托单位：
Gifu Pharmaceutical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1987
资助国家：
日本
起止时间：
1987 至 1988
项目状态：
已结题

项目摘要

Contents of alkaline phosphatase isozymes in human normal tissues were determined by use of monoclonal immunocatalytical assays. Normal tissues contained all three isozymes, the intestinal mucosa, for example, which besides intestinal alkaline phosphatase also expresses trace amounts of placental and liver alkaline phosphatases. Relative high levels of intestional enzyme was also detected in human kindey tissues as well as liver isozyme. Seminoma and control tissues were analyzed for several tumor markers. Very high levels of placental alkaline phosphatase-like enzyme levels were found in all seminomas studied. The majority of the seminomas were of phenotype I, thus differing from placental alkaline phosphatase. The mean amount of enzyme protein as mesured by monoclonal antibodies, was 10-100 times higher than in non-malignant tissues and 10 times lower than in placental tissues. This finding indicates that the entire genome coding for alkaline phosphatase may be activated in seminomas. High levels of placental-like isozyme were also measured in the ovarian cancer and liver metastatis from colon cancer. The cell lines derived from various cancer were found to express the alkaline phosphatase isozymes. In a preliminary experiment, it is found excellent radioimmunolocalization in ovarian cancer tissue can be obtained by use of ^<125>I-labelled monoclonal antibody against placental alkaline phosphatase isozyme.

应用单克隆免疫分析法测定了人正常组织中碱性磷酸酶同工酶的含量。正常组织包含所有三种同工酶，例如肠粘膜，除了肠碱性磷酸酶外，还表达痕量的胎盘和肝脏碱性磷酸酶。在人肾组织和肝组织中也检测到较高水平的肠酶。精原细胞瘤和对照组织分析了几种肿瘤标志物。非常高水平的胎盘碱性磷酸酶样酶的水平被发现在所有的子宫肌瘤研究。大多数腺瘤是表型I，因此不同于胎盘碱性磷酸酶。用单克隆抗体测定的酶蛋白的平均量比非恶性组织高10-100倍，比胎盘组织低10倍。这一发现表明，编码碱性磷酸酶的整个基因组可能在乳腺癌中被激活。在卵巢癌和结肠癌肝转移中也检测到高水平的胎盘样同工酶。发现来源于各种癌症的细胞系表达碱性磷酸酶同工酶。在初步实验中发现，用~（131）<125>I标记的抗胎盘碱性磷酸酶同工酶单克隆抗体对卵巢癌组织可获得良好的放射免疫定位。