Cheung N K, Neely J E, Landmeier B, Nelson D, Miraldi F
Case Western Reserve University School of Medicine, Department of Pediatrics, Cleveland, Ohio.
J Nucl Med. 1987 Oct;28(10):1577-83.
The biodistribution of 3F8, and IgG3 murine monoclonal antibody (MoAb) specific for the disialoganglioside GD2, was studied in nude mice xenografted with human neuroblastoma (NB). 3F8 conjugated to radioactive iodine and injected intravenously localized selectively to seven human NB when compared with Ewing's sarcoma and Hela cell xenograft controls. Uptake in NB was shown to be specific for MoAb 3F8 when contrasted with pooled mouse IgG or irrelevant IgG3 MoAb controls. Both small (50 mg) and large tumors greater than 2 g) showed radiolocalization. The percent injected dose uptake per gram tumor ranged from 8 to 50% and was inversely correlated with tumor size. Optimal tumor to normal tissue ratios were reached by 24-48 hr. There was no abnormal uptake in the reticuloendothelial system and the MoAb did not cross the blood-brain barrier. Based on the kinetics of the amount of radioactivity deposited in tissues, the relative radiation dose to normal organs was estimated to be 1% to 20% of the tumor dose. The MoAb 3F8 is useful for targeting radioactivity to human NB in vivo and the nude mice xenograft model may allow optimization of parameters that influence such biodistribution.
研究了针对双唾液酸神经节苷脂GD2的3F8和IgG3鼠单克隆抗体(MoAb)在接种人神经母细胞瘤(NB)的裸鼠中的生物分布。与尤因肉瘤和Hela细胞异种移植对照相比,与放射性碘结合并静脉注射的3F8选择性地定位于7个人NB。与混合小鼠IgG或无关IgG3 MoAb对照相比,NB中的摄取显示对MoAb 3F8具有特异性。小肿瘤(50 mg)和大于2 g的大肿瘤均显示放射性定位。每克肿瘤的注射剂量摄取百分比范围为8%至50%,且与肿瘤大小呈负相关。24至48小时达到最佳肿瘤与正常组织比率。网状内皮系统没有异常摄取,且MoAb未穿过血脑屏障。根据沉积在组织中的放射性量的动力学,估计正常器官的相对辐射剂量为肿瘤剂量的1%至20%。MoAb 3F8可用于在体内将放射性靶向人NB,裸鼠异种移植模型可能允许优化影响这种生物分布的参数。