首页> 外文OA文献 >188Re-ZHER2:V2, a promising affibody-based targeting agent against HER2-expressing tumors : preclinical assessment
【2h】

188Re-ZHER2:V2, a promising affibody-based targeting agent against HER2-expressing tumors : preclinical assessment

机译:188Re-ZHER2:V2,一种有前途的,基于亲和体的靶向表达药物,针对表达HER2的肿瘤:临床前评估

代理获取
本网站仅为用户提供外文OA文献查询和代理获取服务,本网站没有原文。下单后我们将采用程序或人工为您竭诚获取高质量的原文,但由于OA文献来源多样且变更频繁,仍可能出现获取不到、文献不完整或与标题不符等情况,如果获取不到我们将提供退款服务。请知悉。

摘要

Affibody molecules are small (7 kDa) nonimmunoglobulin scaffold proteins with favorable tumor-targeting properties. Studies concerning the influence of chelators on biodistribution of 99mTc-labeled Affibody molecules demonstrated that the variant with a C-terminal glycyl-glycyl-glycyl-cysteine peptide–based chelator (designated ZHER2:V2) has the best biodistribution profile in vivo and the lowest renal retention of radioactivity. The aim of this study was to evaluate 188Re-ZHER2:V2 as a potential candidate for radionuclide therapy of human epidermal growth factor receptor type 2 (HER2)–expressing tumors. Methods: ZHER2:V2 was labeled with 188Re using a gluconate-containing kit. Targeting of HER2-overexpressing SKOV-3 ovarian carcinoma xenografts in nude mice was studied for a dosimetry assessment. Results: Binding of 188Re-ZHER2:V2 to living SKOV-3 cells was demonstrated to be specific, with an affinity of 6.4 ± 0.4 pM. The biodistribution study showed a rapid blood clearance (1.4 ± 0.1 percentage injected activity per gram [%ID/g] at 1 h after injection). The tumor uptake was 14 ± 2, 12 ± 2, 5 ± 2, and 1.8 ± 0.5 %IA/g at 1, 4, 24, and 48 h after injection, respectively. The in vivo targeting of HER2-expressing xenografts was specific. Already at 4 h after injection, tumor uptake exceeded kidney uptake (2.1 ± 0.2 %IA/g). Scintillation-camera imaging showed that tumor xenografts were the only sites with prominent accumulation of radioactivity at 4 h after injection. Based on the biokinetics, a dosimetry evaluation for humans suggests that 188Re-ZHER2:V2 would provide an absorbed dose to tumor of 79 Gy without exceeding absorbed doses of 23 Gy to kidneys and 2 Gy to bone marrow. This indicates that future human radiotherapy studies may be feasible. Conclusion: 188Re-ZHER2:V2 can deliver high absorbed doses to tumors without exceeding kidney and bone marrow toxicity limits.
机译:Affibody分子是小的(7 kDa)非免疫球蛋白支架蛋白,具有良好的肿瘤靶向特性。关于螯合剂对99mTc标记的Affibody分子生物分布的影响的研究表明,带有C末端基于糖基-糖基-糖基-半胱氨酸肽的螯合剂(命名为ZHER2:V2)的变体在体内具有最佳的生物分布特征,而最低肾脏保留放射性。这项研究的目的是评估188Re-ZHER2:V2作为放射性核素治疗表达人类表皮生长因子受体2型(HER2)的肿瘤的潜在候选药物。方法:使用含葡萄糖酸盐的试剂盒将188Re标记为ZHER2:V2。研究了针对裸鼠中过量表达HER2的SKOV-3卵巢癌异种移植物的剂量,以进行剂量学评估。结果:188Re-ZHER2:V2与活SKOV-3细胞的结合被证明是特异性的,亲和力为6.4±0.4 pM。生物分布研究显示血液清除迅速(注射后1 h,每克注射活性为1.4±0.1%[%ID / g])。注射后1、4、24和48小时,肿瘤摄取分别为14±2、12±2、5±2和1.8±0.5%IA / g。表达HER2的异种移植物的体内靶向是特异性的。注射后4小时,肿瘤摄取已经超过肾脏摄取(2.1±0.2%IA / g)。闪烁照相机成像显示,肿瘤异种移植物是注射后4 h唯一具有明显放射性累积的部位。根据生物动力学,对人体的剂量学评估表明,188Re-ZHER2:V2将为肿瘤提供79 Gy的吸收剂量,而不会超过肾脏的23 Gy和骨髓的2 Gy吸收剂量。这表明未来的人体放射治疗研究可能是可行的。结论:188Re-ZHER2:V2可以向肿瘤提供高吸收剂量,而不会超出肾脏和骨髓的毒性极限。

相似文献

  • 外文文献
  • 中文文献
  • 专利
代理获取

客服邮箱:kefu@zhangqiaokeyan.com

京公网安备:11010802029741号 ICP备案号:京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有
  • 客服微信

  • 服务号