Inorganic Chemistry

Scalable 18F Processing Conditions for Copper-Mediated Radiofluorination Chemistry Facilitate "Design of Experiments" (DoE) Optimization Studies and Afford an Improved Synthesis of [18F]Olaparib.

Andreas Maurer Eberhard Karls University Tuebingen

Abstract

A convenient, scalable, and azeotropic drying free method for processing [18F]fluoride as base free
[18F]TBAF is reported and applied to copper-mediated radiofluorination (CMRF) radiosyntheses. A central
feature of this method is that a single production of [18F]TBAF can be divided into small aliquots that can be
used to perform multiple small-scale reactions in DoE optimization studies. The results of these studies can
then be reliably translated to full batch tracer productions using automated synthesizers. This processing
technique was successfully applied to the manual DoE optimization, DoE study validation, and subsequent
full-batch automation of the PARP-1 tracer [18F]olaparib. After DoE optimization, we were able to produce
[18F]olaparib in high radiochemical yields via both manual (%RCY (CMRF step only) = 78 ± 6 %, n = 4) and
automated (up to 80% radiochemical yield (%RCY); 41% activity yield (%AY)) radiosynthesis procedures.
This work further demonstrates the power of the DoE approach for improving the radiochemical yields and
radiosynthesis performance of clinically relevant tracer productions

Content

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Supplementary material

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QMA SI 1 060521 1