Development of Customized [18F]Fluoride Elution Techniques for the Enhancement of Copper-Mediated Late-Stage Radiofluorination.
In a relatively short period of time, transition metal-mediated radiofluorination reactions have changed the PET radiochemistry landscape. These reactions have enabled the radiofluorination of a wide range of substrates, facilitating access to radiopharmaceuticals that were challenging to synthesize using traditional fluorine-18 radiochemistry. However, the process of adapting these new reactions for automated radiopharmaceutical production has revealed limitations in fitting them into the confines of traditional radiochemistry systems. In particular, the presence of bases (e.g. K2CO3) and/or phase transfer catalysts (PTC) (e.g. kryptofix 2.2.2) associated with fluorine-18 preparation has been found to be detrimental to reaction yields. We hypothesized that these limitations could be addressed through the development of alternate techniques for preparing [18F]fluoride. This approach also opens the possibility that an eluent can be individually tailored to meet the specific needs of a metal-catalyzed reaction of interest. In this communication, we demonstrate that various solutions of copper salts, bases, and ancillary ligands can be utilized to elute [18F]fluoride from ion exchange cartridges. The new procedures are effective for fluorine-18 radiochemistry and, as proof of concept, have been used to optimize an otherwise base-sensitive copper-mediated radiofluorination reaction.
Department of Radiology, University of Michigan Medical School, 1301 Catherine St., Ann Arbor, MI, 48109, USA.
Andrew V
0000-0001-6289-196X
AV
Mossine
Department of Radiology, University of Michigan Medical School, 1301 Catherine St., Ann Arbor, MI, 48109, USA.
Allen F
AF
Brooks
Department of Chemistry, University of Michigan, 930 North University Avenue, Ann Arbor, MI, 48109, USA.
Naoko
N
Ichiishi
Department of Chemistry, University of Michigan, 930 North University Avenue, Ann Arbor, MI, 48109, USA.
Katarina J
KJ
Makaravage
Department of Chemistry, University of Michigan, 930 North University Avenue, Ann Arbor, MI, 48109, USA. mssanfor@umich.edu.
Melanie S
MS
Sanford
Department of Radiology, University of Michigan Medical School, 1301 Catherine St., Ann Arbor, MI, 48109, USA. pjhscott@umich.edu.|Interdepartmental Program in Medicinal Chemistry, University of Michigan, 428 Church St., Ann Arbor, MI, 48109, USA. pjhscott@umich.edu.
Peter J H
PJ
Scott
D002853:Chromatography, Liquid / Q000379:methods*; D003300:Copper / Q000378:metabolism*; D005462:Fluorine Radioisotopes / Q000302:isolation & purification*; D006801:Humans; D049268:Positron-Emission Tomography / Q000379:methods; D019275:Radiopharmaceuticals / Q000302:isolation & purification*; D014131:Trace Elements / Q000378:metabolism*
D005462:Fluorine Radioisotopes; D019275:Radiopharmaceuticals; D014131:Trace Elements; D003300:Copper; C000615276:Fluorine-18