Ullén A, Riklund Ahlström K, Makiya R, Stigbrand T
Department of Immunology and Medical Biochemistry and Biophysics, University of Umeå, Sweden.
Cell Biophys. 1995 Aug;27(1):31-45. doi: 10.1007/BF02822525.
Significant improvements in tumor/nontumor ratio can be achieved by injections of nonlabeled anti-idiotypic monoclonal antibodies (MAbs) during radioimmunolocalization and radioimmunotherapy using MAbs to target experimental tumors. The in vivo effects of an anti-idiotypic MAb (alpha H7) against a radioiodinated, high affinity, low dissociation rate, monoclonal antiplacental alkaline phosphatase antibody (H7) was investigated. Following in vivo injection of the anti-idiotypic MAb, the radioactivity in experimental tumors was found to decrease only 25% while the reduction of corresponding radioactivity in nontumor tissues amounted to 65-85%, compared to the group receiving no anti-idiotypic MAbs. These results indicate that it is possible to partially clear the circulation and nontumor tissues from excess of radiolabeled idiotypic antibody, without significant decrease in specific tumor localization, increasing the tumor/nontumor ratio three- to fourfold. Circulating nontumor targeting radiolabeled antibodies is one of the major limiting factors in radioimmunotherapy today. Injection of anti-idiotypic MAbs could selectively significantly reduce the radiation dose to radio-sensitive tissues, i.e., bone marrow and intestine, thus improving efficiency in radioimmunoscintigraphy and radioimmunotherapy.
在使用单克隆抗体靶向实验性肿瘤进行放射免疫定位和放射免疫治疗期间,通过注射未标记的抗独特型单克隆抗体(MAb),可显著提高肿瘤/非肿瘤比率。研究了一种抗独特型单克隆抗体(αH7)对放射性碘化的、高亲和力、低解离率的单克隆抗胎盘碱性磷酸酶抗体(H7)的体内效应。与未注射抗独特型单克隆抗体的组相比,体内注射抗独特型单克隆抗体后,实验性肿瘤中的放射性仅降低25%,而非肿瘤组织中相应放射性的降低幅度达65% - 85%。这些结果表明,有可能在不显著降低肿瘤特异性定位的情况下,部分清除循环系统和非肿瘤组织中过量的放射性标记独特型抗体,使肿瘤/非肿瘤比率提高三到四倍。循环中的非肿瘤靶向放射性标记抗体是当今放射免疫治疗的主要限制因素之一。注射抗独特型单克隆抗体可选择性地显著降低对放射敏感组织(即骨髓和肠道)的辐射剂量,从而提高放射免疫闪烁成像和放射免疫治疗的效率。