A Design of Experiments (DoE) Approach Accelerates the Optimization of Copper-Mediated 18F-Fluorination Reactions of Arylstannanes
A Design of Experiments (DoE) Approach Accelerates the Optimization of Copper-Mediated 18F-Fluorination Reactions of Arylstannanes
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DOI：
10.1038/s41598-019-47846-6
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发表时间：
2019-08-06
影响因子：
4.6
通讯作者：
Maurer, Andreas
中科院分区：
文献类型：
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作者：
Bowden, Gregory D.;Pichler, Bernd J.;Maurer, Andreas
F-18放射化学的最新进展，如铜介导的放射性同位素（CMRF）化学的出现，为新型化学多样性PET探针提供了前所未有的途径;然而，这些多组分反应带来了一系列新的复杂优化问题。实验设计（DoE）是一种用于过程优化的统计方法，用于各种行业。它具有许多优势，传统上采用的“一个变量在一个时间”（OVAT）的方法，如提高实验效率，以及解决因素的相互作用，并提供详细的过程的行为地图的能力。在这里，我们展示了能源部的效用，新的放射化学方法和新型PET示踪剂合成的发展和优化。使用DoE构建实验有效的因子筛选和优化研究，我们能够识别关键因子并对其行为进行建模，其实验效率比传统的OVAT方法高出两倍以上。此外，DoE的使用使我们能够收集到一些芳基锡烷前体的CMRF行为的新见解。这些信息指导了我们的决策工作，同时开发了适合F-18 PET示踪剂合成独特工艺要求的有效反应条件。
Recent advancements in F-18 radiochemistry, such as the advent of copper-mediated radiofluorination (CMRF) chemistry, have provided unprecedented access to novel chemically diverse PET probes; however, these multicomponent reactions have come with a new set of complex optimization problems. Design of experiments (DoE) is a statistical approach to process optimization that is used across a variety of industries. It possesses a number of advantages over the traditionally employed "one variable at a time" (OVAT) approach, such as increased experimental efficiency as well as an ability to resolve factor interactions and provide detailed maps of a process's behavior. Here we demonstrate the utility of DoE to the development and optimization of new radiochemical methodologies and novel PET tracer synthesis. Using DoE to construct experimentally efficient factor screening and optimization studies, we were able to identify critical factors and model their behavior with more than two-fold greater experimental efficiency than the traditional OVAT approach. Additionally, the use of DoE allowed us to glean new insights into the behavior of the CMRF of a number of arylstannane precursors. This information has guided our decision-making efforts while developing efficient reaction conditions that suit the unique process requirements of F-18 PET tracer synthesis.