A Design of Experiments (DoE) Approach Accelerates the Optimization of Copper-Mediated 18 F-Fluorination Reactions of Arylstannanes

Scientific Reports
Gregory D BowdenAndreas Maurer

Abstract

Recent advancements in 18F 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 effor...Continue Reading

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Citations

Jan 12, 2020·Scientific Reports·Michael E Fassbender
Nov 24, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Gonçalo S ClementePhilip H Elsinga
Sep 20, 2019·Organic & Biomolecular Chemistry·Andrew V MossinePeter J H Scott
Nov 8, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Jo Sing Julia TangRuben R Rosencrantz
Mar 23, 2021·Clinical and Translational Imaging : Reviews in Nuclear Medicine and Molecular Imaging·Jay S WrightPeter J H Scott
Apr 13, 2021·Journal of Fluorine Chemistry·Cassis VarlowNeil Vasdev
Apr 17, 2021·Journal of Hazardous Materials·Darshita Ketan Pandya, Madhava Anil Kumar
May 1, 2021·Materials·Beng Wei ChongMohd Mustafa Al Bakri Abdullah
Jun 3, 2021·Toxics·Maria MihăilescuCristian Ștefan Dumitriu
Jun 21, 2021·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·Alice KasemiireEric Ziemons
May 21, 2020·Molecular Pharmaceutics·Louis Allott, Eric O Aboagye
Nov 20, 2020·The Journal of Physical Chemistry. B·Alexander PlunkettBerta Domènech

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Methods Mentioned

BETA
imaging technique

Software Mentioned

OVAT
DoE
Modde Go
MODDE
JMP

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