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

用单抗免疫催化法测定人正常组织碱性磷酸酶同工酶的含量。正常组织含有所有三种同工酶，例如肠粘膜，除了肠道碱性磷酸酶外，它还表达微量的胎盘和肝脏碱性磷酸酶。在人类肾脏组织和肝脏同工酶中也检测到相对较高的内切酶水平。对精原细胞瘤和对照组织进行了几种肿瘤标志物的分析。在所有研究的精原细胞瘤中都发现了非常高水平的胎盘碱性磷酸酶样酶水平。精原细胞瘤多为I型，与胎盘碱性磷酸酶不同。用单抗测定，酶蛋白的平均含量比非恶性组织高10-100倍，比胎盘组织低10倍。这一发现表明，在精原细胞瘤中，编码碱性磷酸酶的整个基因组可能被激活。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。不同肿瘤来源的细胞系均表达碱性磷酸酶同工酶。在初步实验中，发现用~(125)I标记的抗胎盘碱性磷酸酶同工酶的单抗可以在卵巢癌组织中获得良好的放射免疫定位。

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.