TY - JOUR
T1 - Automated radiosynthesis of 5-[11C]L-glutamine, an important tracer for glutamine utilization
AU - Rosenberg, Adam J.
AU - Nickels, Michael L.
AU - Schulte, Michael L.
AU - Manning, H. Charles
N1 - Publisher Copyright:
© 2018 Elsevier Inc.
PY - 2018/12
Y1 - 2018/12
N2 - Introduction: The natural amino acid L-Glutamine (Gln) is essential for both cell growth and proliferation. In addition to glucose, cancer cells utilize Gln as a carbon source for ATP production, biosynthesis, and as a defense against reactive oxygen species. The utilization of [11C]Gln has been previously reported as a biomarker for tissues with an elevated demand for Gln, however, the previous reports for the preparation of [11C]Gln were found to be lacking several crucial aspects necessary for transition to human production. Namely, the presence of unreacted precursor and the use of non-commercialized, custom built, reaction platforms. Herein, we report the development and utilization of methodology for the automated production of [11C]Gln that meets institutional criteria for human use. Methods: The preparation of [11C]Gln was carried out on the GE FX2N platform. Briefly, after trapping of [11C]HCN with a solution of CsHCO3 in DMF, the [11C]CsCN was reacted with a commercially available precursor. This intermediate was then purified by HPLC and deprotected/hydrolyzed under acidic conditions. Following pH adjustment, the product was filtered to give the desired [11C]Gln as a sterile injectable. The resulting product was then analyzed for quality assurance. Results: Automated production by this method reliably provides over 3.7 GBq (100 mCi) of [11C]Gln. The resulting final drug product was found to have a >99% radiochemical purity, <5% of D-Gln present, no detectable impurities, and the total preparation time was roughly 45 min from the end-of-bombardment. Conclusions: A fast, reliable and efficient automated radiosynthesis was developed using a commercially available module. Purifications used throughout allow for both a radiochemically and chemically pure final product solution of [11C]Gln.
AB - Introduction: The natural amino acid L-Glutamine (Gln) is essential for both cell growth and proliferation. In addition to glucose, cancer cells utilize Gln as a carbon source for ATP production, biosynthesis, and as a defense against reactive oxygen species. The utilization of [11C]Gln has been previously reported as a biomarker for tissues with an elevated demand for Gln, however, the previous reports for the preparation of [11C]Gln were found to be lacking several crucial aspects necessary for transition to human production. Namely, the presence of unreacted precursor and the use of non-commercialized, custom built, reaction platforms. Herein, we report the development and utilization of methodology for the automated production of [11C]Gln that meets institutional criteria for human use. Methods: The preparation of [11C]Gln was carried out on the GE FX2N platform. Briefly, after trapping of [11C]HCN with a solution of CsHCO3 in DMF, the [11C]CsCN was reacted with a commercially available precursor. This intermediate was then purified by HPLC and deprotected/hydrolyzed under acidic conditions. Following pH adjustment, the product was filtered to give the desired [11C]Gln as a sterile injectable. The resulting product was then analyzed for quality assurance. Results: Automated production by this method reliably provides over 3.7 GBq (100 mCi) of [11C]Gln. The resulting final drug product was found to have a >99% radiochemical purity, <5% of D-Gln present, no detectable impurities, and the total preparation time was roughly 45 min from the end-of-bombardment. Conclusions: A fast, reliable and efficient automated radiosynthesis was developed using a commercially available module. Purifications used throughout allow for both a radiochemically and chemically pure final product solution of [11C]Gln.
KW - Automated radiosynthesis
KW - Carbon-11
KW - Metabolism
KW - PET
KW - Radiopharmaceuticals
KW - [C]Glutamine
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U2 - 10.1016/j.nucmedbio.2018.09.002
DO - 10.1016/j.nucmedbio.2018.09.002
M3 - Article
C2 - 30359787
AN - SCOPUS:85055164775
SN - 0969-8051
VL - 67
SP - 10
EP - 14
JO - Nuclear Medicine and Biology
JF - Nuclear Medicine and Biology
ER -