@inproceedings{oai:repo.qst.go.jp:00086460,
 author = {Masayuki, Fujinaga and Kurihara, Yusuke and Masanao, Ogawa and Katsushi, Kumata and Wakana, Mori and Zhang, Ming-Rong and Masayuki, Fujinaga and Kurihara, Yusuke and Masanao, Ogawa and Katsushi, Kumata and Wakana, Mori and Zhang, Ming-Rong},
 book = {Nuclear Medicine and Biology},
 month = {Jun},
 note = {Objectives: L-Glutamine is involved in various metabolic processes. Recently, glutaminolysis has been recognized to play important roles in activation of many cancer cells. Thus, [11C]L-glutamine is a useful PET tracer for elucidating the mechanisms of glutamine utilization in cancer cells. To date, synthesis of [11C]L-glutamine has been reported by several groups [1]. However, their synthesis methods required long synthesis time (60 min) and complicated synthesis device for separating and purifying the reaction mixture by solid phase extractions and HPLC system. Herein, we developed a simple and rapid method for synthesizing [11C]L-glutamine using a fully-automated synthesis system without HPLC purification. 
Methods: [11C]L-glutamine was synthesized by using a fully-automated synthesis system (Scheme 1). The precursor 1 was purchased from commercial sources. Before irradiation of [11C]CO2, the mixture of 18-crown-6 (8 mg in 900 L of CH3CN) and Cs2CO3 (3 mg in 150 L of water) was azeotropically dried in reaction vial and then added CH3CN (300 L). After the automatically produced [11C]HCN was trapped into the above solution, precursor 1 (3.5 mg) in CH3CN (300 L) was added and the reaction mixture was heated at 90 oC for 8 min, followed by complete removal of the reaction solvent. TFA-H2SO4 (4 : 1, 500 L) was added to the residue and this reaction mixture was heated at 80 oC for 5 min. After the reaction, the mixture was diluted with diethyl ether (1.5 mL) and passed through a silica plus Sep-Pak cartridge to trap [11C]L-glutamine. The cartridge was washed with diethyl ether (10 mL) and then eluted with phosphate buffer (5 mL). The [11C]L-glutamine solution was obtained by removal of diethyl ether from the eluant and was adjusted to suitable pH value for use by addition of phosphate buffer (4 mL). The final radioactive product was analyzed by HPLC with radioactivity and UV-VIS detectors.
 

Scheme 1. Syntheses of [11C]L-glutamine
Results: The [11C]cyanation of precursor 1 in CH3CN was smoothly proceeded in excellent yields. To efficiently perform the deprotection and amidation of cyano group for [11C]2, removal of CH3CN was carried out at 100 oC for 7 min after the [11C]cyanation. Despite of the presence of unreacted 1, reaction of [11C]2 and TFA-H2SO4 was successfully proceeded without serious side product. However, it was found that peek tube equipped in the automated module was melted due to use of strong acids. Changing the strong acids to TFA-H2SO4 (8 : 1) or HCl decreased the yield of [11C]L-glutamine. This problem was solved by replacing the peek tube with the Teflon tube. Finally, [11C]L-glutamine was obtained in 27±7% (n = 5) radiochemical yield at the end of irradiation and >85% radiochemical purity. The fully-automated synthesis time from the end of bombardment was 45 min. We obtained [11C]L-glutamine with sufficient radioactivity and radiochemical purity for application study.
Conclusions: We have developed a simple and rapid method for the synthesis of [11C]L-glutamine using a fully-automated synthesis system. Improvement for the radiochemical purity of [11C]L-glutamine is in progress.},
 publisher = {Elsevier Ltd.},
 title = {Simple and rapid automated synthesis of [11C]L-glutamine},
 year = {2022}
}