Klein J L, Nguyen T H, Laroque P, Kopher K A, Williams J R, Wessels B W, Dillehay L E, Frincke J, Order S E, Leichner P K
Johns Hopkins Oncology Center, Department of Radiation Oncology, Baltimore, Maryland 21205.
Cancer Res. 1989 Nov 15;49(22):6383-9.
Therapeutic trials were performed on the HepG2 human hepatoblastoma implanted s.c. in the athymic nude mouse. Animals were treated with polyclonal and monoclonal antiferritin and control antibodies labeled with either iodine-131 (131I) or yttrium-90 (90Y). Administration of 400 muCi of 131I-labeled polyclonal antiferritin or 300 muCi of 90Y-labeled polyclonal antiferritin significantly increased survival (P less than 0.001). There were no tumor cures with radiolabeled polyclonal antibody therapy. Animals treated with 200 or 300 muCi of 131I-labeled monoclonal antiferritin (QCI054) did not show increased survival compared to controls. Although 400 muCi of 131I-labeled QCI significantly prolonged survival, treatment resulted in no long-term survivors. Monoclonal antiferritin labeled with 90Y significantly prolonged survival of animals (P less than 0.001) at doses of 100, 200, or 300 muCi compared with untreated controls. Fifty % of the animals treated with 200 muCi and 75% of the animals treated with 300 muCi showed no evidence of disease at 140 days following treatment. Four hundred muCi of 90Y-labeled QCI proved toxic to the animals. Increased survival was accompanied by a decrease in tumor mitotic rate and increase in cellular polymorphism as determined by pathological examination. The radiation dose absorbed in the tumor correlated directly with tumor response following treatment. The absorbed dose in tumors for complete decay of the isotope ranged from 165 and 330 cGy at the periphery and center of small tumors for an administered activity of 200 muCi of 131I-labeled polyclonal antiferritin, to 7,573 and 12,400 cGy for 300 muCi of 90Y-labeled monoclonal antiferritin QCI.
对接种于无胸腺裸鼠皮下的人肝癌细胞系HepG2进行了治疗试验。用多克隆和单克隆抗铁蛋白抗体以及用碘-131（131I）或钇-90（90Y）标记的对照抗体对动物进行治疗。给予400μCi的131I标记的多克隆抗铁蛋白或300μCi的90Y标记的多克隆抗铁蛋白可显著提高生存率（P<0.001）。放射性标记的多克隆抗体治疗未实现肿瘤治愈。与对照组相比，用200或300μCi的131I标记的单克隆抗铁蛋白（QCI054）治疗的动物未显示出生存率增加。尽管400μCi的131I标记的QCI显著延长了生存期，但治疗后没有长期存活者。与未治疗的对照组相比，用90Y标记的单克隆抗铁蛋白在100、200或300μCi剂量下显著延长了动物的生存期（P<0.001）。用200μCi治疗的动物中有50%以及用300μCi治疗的动物中有75%在治疗后140天未显示疾病迹象。400μCi的90Y标记的QCI对动物有毒性。通过病理检查确定，生存率的提高伴随着肿瘤有丝分裂率的降低和细胞多态性的增加。肿瘤吸收的辐射剂量与治疗后的肿瘤反应直接相关。对于给予200μCi的131I标记的多克隆抗铁蛋白，小肿瘤周边和中心的同位素完全衰变时肿瘤吸收剂量范围为165至330cGy，而对于300μCi的90Y标记的单克隆抗铁蛋白QCI，吸收剂量为7573至12400cGy。
