利西诺普利尔放射结合物的开发,用于对血管酶转化酶的核成像
Christian Vaccarin1, Darja Beyer1, Anzhelika Moiseeva1
1Center for Radiopharmaceutical Sciences, PSI Center for Life Sciences, Villigen-PSI, Switzerland.
概括
基于lysinopril的放射性结合物被开发用于血管素转化酶 (ACE) 的核成像. [67Ga]Ga-DOTA-LIS-02在小鼠中的ACE可视化方面显示出有希望的结果.
科学领域:
- 放射化学和核医学 放射化学和核医学
- 分子成像学分子成像学
- 心血管研究研究心血管研究
背景情况:
- ангиотензин转化酶 (ACE) 在心血管平衡中起着至关重要的作用.
- ACE 功能障碍与各种病理状况有关,需要有效的成像策略.
- 利西诺普里尔是一种ACE抑制剂,具有针对性分子成像的潜力.
研究的目的:
- 开发和评估基于lysinopril的放射性结合物用于ACE的核成像.
- 评估新型放射性结合物的稳定性,细胞吸收和组织分布.
- 为了确定在体内可视化ACE表达的可行性.
主要方法:
- 用-67.7合成和放射性标记西诺普利结合物 (DOTA-LIS-01,DOTA-LIS-02,NODAGA-LIS-02) 和.
- 在盐水和生物血中进行体外稳定性评估.
- 在HEK细胞和分子动力学研究中评估ACE介导的细胞吸收.
- 在携带HEK-ACE异种移植的小鼠体内组织分布研究和核成像.
主要成果:
- 放射性结合物DOTA-LIS-01,DOTA-LIS-02和NODAGA-LIS-02在高纯度下进行了合成,并有效地进行了放射性标记.
- [67Ga]Ga-DOTA-LIS-02和[67Ga]Ga-NODAGA-LIS-02在实验室中表现出良好的稳定性.
- 与[67Ga]Ga-DOTA-LIS-01相比,观察到[67Ga]Ga-DOTA-LIS-02和[67Ga]Ga-NODAGA-LIS-02的细胞吸收率更高,这是由于链接器的长度.
- 核成像证实了异种移植的吸收,其中[67Ga]Ga-DOTA-LIS-02显示了较高的积累 (14%IA/g在1小时).
- 活体研究证实[67Ga]Ga-DOTA-LIS-02在小鼠肺部和脏中的ACE特定结合.
结论:
- [67Ga]Ga-DOTA-LIS-02被确定为在临床前模型中可视化ACE的最有前途的放射结合物.
- 开发的放射性结合物具有在病理生理条件下评估ACE表达动态的潜力.
- 需要进一步的临床前和临床研究来验证其诊断效用.
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