Buchsbaum D J, ten Haken R K, Heidorn D B, Lawrence T S, Glatfelter A A, Terry V H, Guilbault D M, Steplewski Z, Lichter A S
Department of Radiation Oncology, University of Michigan, Ann Arbor 48109.
Int J Radiat Oncol Biol Phys. 1990 May;18(5):1033-41. doi: 10.1016/0360-3016(90)90438-p.
Inhibition of growth of LS174T human colon cancer xenografts in athymic nude mice due to 131I-labeled MoAb 17-1A treatment was compared to inhibition due to different single doses of 60Co external radiation. From those data, conditions which produced equivalent radiobiological end points could be identified and compared to dose estimates calculated using a technique analogous to the Medical Internal Radiation Dose (MIRD) Committee formalism. The tumor growth rate in mice injected with a single intraperitoneal administration of 300 microCi of 131I-labeled MoAb was reduced relative to tumor growth in untreated control animals and in mice administered unlabeled MoAb and was found to be similar to the growth rate of tumors given a single 6 Gy dose of 60Co radiation. Furthermore, the growth rate of tumors in mice that received three injections of 300 microCi of 131I-labeled MoAb on days 9, 16 and 28 after tumor cell injection was similar to the growth rate of tumors given a single 60Co dose of 8 or 10 Gy. The biodistribution data for 125I-labeled 17-1A MoAb were used to calculate total doses for the tumor and various normal tissues in animals given a single administration of 131I-labeled 17-1A MoAb. The absorbed radiation dose in tumor was approximately five times higher than in normal tissues. The results of the present study indicate that the tumor growth inhibition produced by the administration of radiolabeled antibody can equal that produced by up to 10 Gy of external beam radiation. In addition, the MIRD calculations allow comparison of this form of low dose radiation to external photon irradiation.
将131I标记的单克隆抗体17 - 1A治疗对无胸腺裸鼠体内LS174T人结肠癌异种移植瘤生长的抑制作用,与不同单剂量60Co外照射的抑制作用进行了比较。根据这些数据,可以确定产生等效放射生物学终点的条件,并与使用类似于医学内照射剂量(MIRD)委员会形式的技术计算出的剂量估计值进行比较。相对于未治疗的对照动物以及注射未标记单克隆抗体的小鼠,单次腹腔注射300微居里131I标记单克隆抗体的小鼠肿瘤生长速率降低,且发现其与接受单次6 Gy剂量60Co辐射的肿瘤生长速率相似。此外,在肿瘤细胞注射后第9、16和28天接受三次300微居里131I标记单克隆抗体注射的小鼠肿瘤生长速率,与接受单次8或10 Gy 60Co剂量的肿瘤生长速率相似。利用125I标记的17 - 1A单克隆抗体的生物分布数据,计算了单次注射131I标记的17 - 1A单克隆抗体的动物肿瘤和各种正常组织的总剂量。肿瘤的吸收辐射剂量大约比正常组织高五倍。本研究结果表明,给予放射性标记抗体所产生的肿瘤生长抑制作用可等同于高达10 Gy外照射所产生的抑制作用。此外,MIRD计算允许将这种低剂量辐射形式与外照射光子辐射进行比较。