排序酶介导的特定位点的结合,以制备-18标记的纳米体
Falguni Basuli1, Jianfeng Shi1, Eric Lindberg1
1Chemistry and Synthesis Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Rockville, Maryland 20892-0001, United States.
Bioconjugate chemistry
|August 22, 2024
概括
我们开发了一种新的,网站特定的方法,用-18 (18F) 标记纳米体 (Nbs),用于分子成像. 这种基于排序酶的方法提供了高产量和纯度,使18F标记的Nbs适合临床前和临床研究.
科学领域:
- 放射化学 放射化学是指辐射化学.
- 分子成像学分子成像学
- 生物结合的生物结合
背景情况:
- 单域抗体,或纳米体 (Nbs),是有价值的分子成像,因为他们的亲和力,特异性,和快速的血液清除.
- 由于Nbs的半衰期很短,因此需要与短寿命的放射性同位素配对,例如-18 (18F),这是临床成像中常见的选择.
- 现有的标签方法可能缺乏效率或特异性,这给基于Nb的成像剂开发带来了挑战.
研究的目的:
- 开发和验证一种新的,基于排序酶的,特定地点的纳米体18F标记方法.
- 评估通过新方法生产的18F标记纳米体的效率,产量,纯度和稳定性.
- 证明制备纳米体成像剂的方法的可通用性,用于临床前和临床应用.
主要方法:
- 用一种索尔塔酶介导的结合策略,对三个不同的纳米体进行特定位置的18F标记.
- 研究了两种标签方法:一间接放射性标签方法和直接标签方法.
- 对标记的纳米体进行了放射化学产量,纯度,特定活动和在生理条件下的稳定性评估.
主要成果:
- 这种新方法在50-70分钟内实现了15-43% (间接) 和23-58% (直接) 的整体放射化学产量.
- 放射化学纯度始终超过98%,所有测试的纳米体的特定活动范围在400-600Ci/mmol之间.
- 标有18F的纳米体在生理条件下表现出极好的稳定性.
结论:
- 开发的基于sortase的,网站特定的18F标记方法对于纳米体来说是简单的,可复制的和可概括的.
- 这种方法促进了高纯度,高特异性活性18F标记纳米体 (Nb-Al[18F]F-RESCA) 的有效制备.
- 该方法易于适应用于使用纳米体或其他小型生物分子的临床前和临床分子成像研究.
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