Scalable F processing conditions for copper-mediated radiofluorination chemistry facilitate DoE optimization studies and afford an improved synthesis of [F]olaparib

• Published in: Organic & biomolecular chemistry 2021-08, Vol.19 (32), p.6995-7
• Main Authors: Bowden, Gregory D, Chailanggar, Nantanat, Pichler, Bernd J, Maurer, Andreas
• Format: Article
• Language: English
• ISSN: 1477-0520; 1477-0539
• DOI: 10.1039/d1ob00903f

A convenient and scalable base-free method for processing [ 18 F]fluoride as [ 18 F]TBAF is reported and applied to copper-mediated radiofluorination radiosyntheses. A central feature of this method is that a single production of [ 18 F]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. The processing method was applied to the DoE optimization of [ 18 F]olaparib, affording the tracer in high radiochemical yields via both manual (%RCY = 78 ± 6%, n = 4 (CMRF step only)) and automated (up to 80% (%RCY); 41% activity yield (%AY)) radiosynthesis procedures. Simple, fast and reliable [ 18 F]fluoride processing that is compatible with both "aliquoted" small-scale DoE optimization and "full-batch" automated radiosyntheses.