使用型氨酸酶和由菌株促进的氧化控制的1,2-农循环添加的场所选择性放射标记
Cindy Rodriguez1,2,3, Samantha Delaney2,3,4, Joni Sebastiano2,3,4
1PhD Program in Chemistry, Graduate Center of the City University of New York New York New York 10016 USA bz102@hunter.cuny.edu.
RSC advances
|June 14, 2023
概括
这项研究引入了一种名为-89的放射性免疫结合物,用于癌症成像. 这种新方法提供了高产量和特异性活性,在结直肠癌模型中显示出有希望的体内行为.
科学领域:
- 生物结合化学 生物结合化学
- 放射性药物开发 放射性药物开发
- 免疫学 免疫学 免疫学
背景情况:
- 选择性抗体修饰对于开发向放射性药物至关重要.
- 传统的放射性标记方法可能会导致异质的产品和效率降低.
- A33抗原是结直肠癌治疗的验证标.
研究的目的:
- 开发和表征一种新的89Zr标记的放射性免疫结合物,使用选择性生物结合策略.
- 评估新型放射性免疫结合物的体外和体内性能.
- 评估这种方法在结直肠癌成像中的潜力.
主要方法:
- 通过铁酶氧化和菌株促进的氧化控制的1,2-农循环添加,对huA33抗体的选择性修饰.
- 与德斯费里奥胺 (DFO) 化剂的结合.
- 在小鼠结直肠癌模型中使用89Zr进行放射标记和体外/体内表征.
主要成果:
- 成功合成了DFO-SPOCQhuA33具有保留的抗原结合亲和力和减少的FcγRI亲和力.
- 实现了89Zr标记放射性免疫结合物[89Zr]Zr-DFO-SPOCQhuA33.33.A33的高产量和特异性活性.
- 在人类结直肠癌的小鼠模型中表现出极好的体内行为.
结论:
- 开发的选择性生物结合策略使得能够产生明确的89Zr标记的放射性免疫结合物.
- 这种新型的放射性免疫结合物在向癌症成像中表现出有希望的特性.
- 这种方法有助于推进下一代治疗药物开发的潜力.
相关概念视频
01:17Oxidation of Phenols to Quinones
In the presence of oxidizing agents, phenols are oxidized to quinones. Quinones can be easily reduced back to phenols using mild reducing agents. The electron-donating hydroxyl group enhances the reactivity of the aromatic ring, enabling oxidation of the ring even in the absence of an α hydrogen.
o-hydroxy phenols are oxidized to o-quinones and p-hydroxy phenols to p-quinones. Such redox reactions involve the transfer of two electrons and two protons. The reversible redox property is crucial in...
o-hydroxy phenols are oxidized to o-quinones and p-hydroxy phenols to p-quinones. Such redox reactions involve the transfer of two electrons and two protons. The reversible redox property is crucial in...
01:12Cycloaddition Reactions: MO Requirements for Photochemical Activation
Some cycloaddition reactions are activated by heat, while others are initiated by light. For example, a [2 + 2] cycloaddition between two ethylene molecules occurs only in the presence of light. It is photochemically allowed but thermally forbidden.