开发和临床前表征一种新型的辐射耐受性EphA2-向的双循环
Mohamed El Fakiri1,2,3, Anusha R Regupathy4, Lisa Uhlmann1,2
1Department of Nuclear Medicine, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Hugstetter Str. 55, 79106 Freiburg, Germany.
Theranostics
|September 6, 2024
概括
一种新型的双循环,BCY18469,有效地向产生素的肝细胞受体A2 (EphA2) 用于放射性应用. 这种药物表现出高亲和力,特异性瘤吸收和良好的清除,支持其在癌症治疗中的潜力.
科学领域:
- 在瘤学瘤学.
- 放射化学 放射化学是指辐射化学.
- 分子成像学分子成像学
背景情况:
- 产生红素的肝细胞受体A2 (EphA2) 是一种受体氨酸激酶在各种瘤中过度表达,与预后不佳相关.
- EphA2 是一个有前途的目标,用于theranostic应用,低分子量基架显示高亲和力和组织透.
- 双循环提供增强的稳定性和类似抗体的亲和性,使它们成为针对性治疗的合适替代品.
研究的目的:
- 开发和评估 BCY18469 ,一种基于双循环的新型放射性射剂,向EphA2.2.
- 评估BCY18469在成像和潜在的治疗应用中的体外和体内临床前性能.
主要方法:
- 通过菌体显示识别和优化BCY18469,然后用68Ga,177Lu和111In进行放射标记.
- 在体外研究中评估了物理化学性质,结合亲和力,内化和特异性.
- 活体PET/MR和SPECT/CT成像和生物分布研究在过度表达EphA2的异种移植小鼠模型中进行.
主要成果:
- BCY18469对人类和小鼠的EphA2 (分别为1.9和3.8nM) 具有很高的结合亲和力,并专门内化到表达EphA2的细胞中.
- PET/MR成像显示了瘤的快速和高缩 (下午1小时1.7 g/mL的SUV. 在HT1080异种移植中) 具有早期对比度和介导清除.
- 生物分布研究证实了高早期瘤吸收率 (19.5±3.5%ID/g在下午1小时). 在HT1080异种移植中),通过SPECT/CT成像进一步验证.
结论:
- BCY18469表现出高亲和力,特定的EphA2向性,以及具有干净度的有利生物分布特征.
- 这些发现凸显了双循环在推进放射性剂方面的潜力.
- 鼓励进一步的翻译研究,以探索BCY18469在癌症治疗中的临床实用性.
相关概念视频
01:22Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal
Erythropoietin-producing hepatocellular carcinoma receptor (Eph) and its ligand, Eph receptor-interacting protein (Ephrin) were first discovered in the human carcinoma cell line, hence the name. Ephrin-Eph interaction guides cells to reach their appropriate location in adult tissues. They also play an essential role in the immune system by helping in immune cell migration, adhesion, and activation. Based on their structure and function, Eph is divided into two classes — EphA and EphB.
01:17Hepatic Drug Excretion: Enterohepatic Cycling
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Post-release drugs and metabolites can be reabsorbed into the body from the intestine. For conjugated metabolites like glucuronides, reabsorption requires enzymatic hydrolysis by intestinal microflora. This...
Post-release drugs and metabolites can be reabsorbed into the body from the intestine. For conjugated metabolites like glucuronides, reabsorption requires enzymatic hydrolysis by intestinal microflora. This...