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Development of High-Throughput Experimentation Approaches for Rapid Radiochemical Exploration.

E William WebbKevin ChengWade P WintonBrandon J C KleinGregory David BowdenMami HorikawaS Wendy LiuJay S WrightStefan VerhoogDipannita KalyaniMichael WismerShane W KrskaMelanie S SanfordPeter J H Scott
Published in: Journal of the American Chemical Society (2024)
Positron emission tomography is a widely used imaging platform for studying physiological processes. Despite the proliferation of modern synthetic methodologies for radiolabeling, the optimization of these reactions still primarily relies on inefficient one-factor-at-a-time approaches. High-throughput experimentation (HTE) has proven to be a powerful approach for optimizing reactions in many areas of chemical synthesis. However, to date, HTE has rarely been applied to radiochemistry. This is largely because of the short lifetime of common radioisotopes, which presents major challenges for efficient parallel reaction setup and analysis using standard equipment and workflows. Herein, we demonstrate an effective HTE workflow and apply it to the optimization of copper-mediated radiofluorination of pharmaceutically relevant boronate ester substrates. The workflow utilizes commercial equipment and allows for rapid analysis of reactions for optimizing reactions, exploring chemical space using pharmaceutically relevant aryl boronates for radiofluorinations, and constructing large radiochemistry data sets.
Keyphrases
  • high throughput
  • positron emission tomography
  • computed tomography
  • electronic health record
  • single cell
  • high resolution
  • big data
  • machine learning
  • mass spectrometry
  • artificial intelligence
  • deep learning