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Title: 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. K 2CO 3) 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 we present here are effective for fluorine-18 radiochemistry and, as proof of concept, have been used to optimize an otherwise base-sensitive copper-mediated radiofluorination reaction.
Authors:
ORCiD logo [1] ;  [1] ;  [2] ;  [2] ;  [2] ;  [3]
  1. Univ. of Michigan Medical School, Ann Arbor, MI (United States). Dept. of Radiology
  2. Univ. of Michigan, Ann Arbor, MI (United States). Dept. of Chemistry
  3. Univ. of Michigan Medical School, Ann Arbor, MI (United States). Dept. of Radiology and Interdepartmental Program in Medicinal Chemistry
Publication Date:
Grant/Contract Number:
SC0012484; R01EB021155
Type:
Accepted Manuscript
Journal Name:
Scientific Reports
Additional Journal Information:
Journal Volume: 7; Journal Issue: 1; Journal ID: ISSN 2045-2322
Publisher:
Nature Publishing Group
Research Org:
Univ. of Michigan, Ann Arbor, MI (United States)
Sponsoring Org:
USDOE; National Institutes of Health (NIH); Merck and Company, Inc., Kenilworth, NJ (United States)
Country of Publication:
United States
Language:
English
Subject:
38 RADIATION CHEMISTRY, RADIOCHEMISTRY, AND NUCLEAR CHEMISTRY; Nuclear chemistry, organic chemistry
OSTI Identifier:
1425386

Mossine, Andrew V., Brooks, Allen F., Ichiishi, Naoko, Makaravage, Katarina J., Sanford, Melanie S., and Scott, Peter J. H.. Development of Customized [18F]Fluoride Elution Techniques for the Enhancement of Copper-Mediated Late-Stage Radiofluorination. United States: N. p., Web. doi:10.1038/s41598-017-00110-1.
Mossine, Andrew V., Brooks, Allen F., Ichiishi, Naoko, Makaravage, Katarina J., Sanford, Melanie S., & Scott, Peter J. H.. Development of Customized [18F]Fluoride Elution Techniques for the Enhancement of Copper-Mediated Late-Stage Radiofluorination. United States. doi:10.1038/s41598-017-00110-1.
Mossine, Andrew V., Brooks, Allen F., Ichiishi, Naoko, Makaravage, Katarina J., Sanford, Melanie S., and Scott, Peter J. H.. 2017. "Development of Customized [18F]Fluoride Elution Techniques for the Enhancement of Copper-Mediated Late-Stage Radiofluorination". United States. doi:10.1038/s41598-017-00110-1. https://www.osti.gov/servlets/purl/1425386.
@article{osti_1425386,
title = {Development of Customized [18F]Fluoride Elution Techniques for the Enhancement of Copper-Mediated Late-Stage Radiofluorination},
author = {Mossine, Andrew V. and Brooks, Allen F. and Ichiishi, Naoko and Makaravage, Katarina J. and Sanford, Melanie S. and Scott, Peter J. H.},
abstractNote = {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 we present here are effective for fluorine-18 radiochemistry and, as proof of concept, have been used to optimize an otherwise base-sensitive copper-mediated radiofluorination reaction.},
doi = {10.1038/s41598-017-00110-1},
journal = {Scientific Reports},
number = 1,
volume = 7,
place = {United States},
year = {2017},
month = {3}
}