Mehta M P, Kubsad S S, Fowler J F, Verma A K, Hsieh J T, Kinsella T J
Department of Human Oncology, Wisconsin Clinical Cancer Center University of Wisconsin, Madison, WI 53792.
Int J Radiat Oncol Biol Phys. 1990 Sep;19(3):627-31. doi: 10.1016/0360-3016(90)90489-7.
Nude mice xenografted with a human pancreatic carcinoma cell line were injected with yttrium-90 (90Y) conjugated to diethylene triaminepenta acetic acid (DTPA) alone, and DTPA covalently linked to a monoclonal antibody, B72.3. The animals were sacrificed in temporal sequence to evaluate isotope distribution. Dosimetry was carried out using the principles outlined in MIRD and ICRU Report 32. Results are expressed as percent uptake per unit mass in organs and tumor and as relative absorbed dose normalized to 90Y uptake in liver at 7 hr. When conjugated to B72.3, an 8-fold increase in isotope localization in the tumor was noted by 24 hr. When the relative absorbed dose is calculated for 90Y and 90Y.B72.3, a 26-fold increase in tumor dose is noted for the 90Y conjugate. Normal tissues show no to modest (less than 5x) enhanced dose with 90Y.B72.3. B72.3, therefore, deserves further investigation as a potential monoclonal antibody for targeting therapeutic radioisotopes and possibly diagnostic radioisotopes to pancreatic cancer. Radiobiological aspects of the low dose rates from radioimmunotherapy are discussed.
将人胰腺癌细胞系移植到裸鼠体内，分别向其注射单独与二乙烯三胺五乙酸（DTPA）偶联的钇-90（90Y），以及与单克隆抗体B72.3共价连接的DTPA。按时间顺序处死动物以评估同位素分布。剂量测定按照医学内照射剂量（MIRD）和国际辐射单位与测量委员会（ICRU）第32号报告中概述的原则进行。结果以器官和肿瘤中每单位质量的摄取百分比以及相对于7小时时肝脏中90Y摄取量的相对吸收剂量表示。当与B72.3偶联时，到24小时时肿瘤中的同位素定位增加了8倍。当计算90Y和90Y.B72.3的相对吸收剂量时，90Y偶联物的肿瘤剂量增加了26倍。正常组织在使用90Y.B72.3时剂量无增加或仅有适度增加（小于5倍）。因此，B72.3作为一种潜在的单克隆抗体，用于将治疗性放射性同位素以及可能的诊断性放射性同位素靶向胰腺癌，值得进一步研究。本文还讨论了放射免疫治疗低剂量率的放射生物学方面。
