Department of Radiation Physics, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Cancer Biother Radiopharm. 2013 Mar;28(2):108-14. doi: 10.1089/cbr.2012.1281. Epub 2012 Dec 11.
Abstract Purpose: Pretargeted radioimmunotherapy (PRIT) against intraperitoneal (i.p.) ovarian microtumors using avidin-conjugated monoclonal antibody MX35 (avidin-MX35) and (211)At-labeled, biotinylated, succinylated poly-l-lysine ((211)At-B-PLsuc) was compared with conventional radioimmunotherapy (RIT) using (211)At-labeled MX35 in a nude mouse model.
Mice were inoculated i.p. with 1×10(7) NIH:OVCAR-3 cells. After 3 weeks, they received PRIT (1.0 or 1.5 MBq), RIT (0.9 MBq), or no treatment. Concurrently, 10 additional animals were sacrificed and examined to determine disease progression at the start of therapy. Treated animals were analyzed with regard to presence of tumors and ascites (tumor-free fraction; TFF), 8 weeks after therapy.
Tumor status at baseline was advanced: 70% of sacrificed animals exhibited ascites. The TFFs were 0.35 (PRIT 1.0 MBq), 0.45 (PRIT 1.5 MBq), and 0.45 (RIT). The 1.5-MBq PRIT group exhibited lower incidence of ascites and fewer tumors >1 mm than RIT-treated animals.
PRIT was as effective as RIT with regard to TFF; however, the size distribution of tumors and presence of ascites indicated that 1.5-MBq PRIT was more efficient. Despite advanced disease in many animals at the time of treatment, PRIT demonstrated good potential to treat disseminated ovarian cancer.
使用亲和素偶联的单克隆抗体 MX35(亲和素-MX35)和(211)At 标记的、生物素化的、琥珀酰化聚赖氨酸((211)At-B-PLsuc)进行靶向放射性免疫治疗(PRIT),与使用(211)At 标记的 MX35 的常规放射性免疫治疗(RIT)进行比较,在裸鼠模型中针对腹腔(i.p.)卵巢微肿瘤。
将 1×10(7) NIH:OVCAR-3 细胞腹腔接种小鼠。3 周后,它们接受 PRIT(1.0 或 1.5 MBq)、RIT(0.9 MBq)或不治疗。同时,另外 10 只动物被处死并检查,以确定治疗开始时疾病的进展情况。治疗动物在治疗 8 周后分析是否存在肿瘤和腹水(肿瘤无进展分数;TFF)。
基线时肿瘤状态为晚期:70%处死的动物出现腹水。TFF 分别为 0.35(PRIT 1.0 MBq)、0.45(PRIT 1.5 MBq)和 0.45(RIT)。1.5-MBq PRIT 组的腹水发生率较低,肿瘤 >1mm 的数量也少于 RIT 治疗组。
就 TFF 而言,PRIT 与 RIT 一样有效;然而,肿瘤的大小分布和腹水的存在表明 1.5-MBq PRIT 更有效。尽管许多动物在治疗时已经处于晚期疾病,但 PRIT 显示出治疗播散性卵巢癌的良好潜力。