synthesis of carbon-11 labelled L-glutamine on Synthra HCN synthesis module

Objectives: Glutaminolysis is a metabolic pathway deployed by many types of cancers including the highly aggressive triple negative breast cancers as a means to utilize glutamine for survival and growth. In our institution, we study the utility of [18F](2S,4R)4-fluoroglutamine and [11C]L-glutamine in various cancers under different interventions. The automation of [18F](2S,4R)4-fluoroglutamine has been previously reported. Here we sought to automate the synthesis of [11C]L-glutamine onto a commercially available Synthra HCN synthesis module to improve the convenience, reliability and feasibility of using this radiotracer in preclinical and clinical studies. Methods: This PET tracer was automated on a commercially available Synthra HCN synthesis module; the synthesis script was initially developed based on the radiolabeling conditions from manual runs. Multiple test runs were performed to optimize the synthesis. All the required chemicals are pre-loaded on the module before the synthesis. The [11C]CO2 generated from the cyclotron was trapped in a CO2 trap on the Synthra HCN module at -180 °C. The resultant [11C]CO2 was then converted to [11C]CH4 by passing [11C]CO2 through nickel column under hydrogen flow at 420 °C. The resulting [11C]CH4 was passed through platinum column heated to 1000 °C by mixing with anhydrous ammonia to obtain [11C]cyanide which was trapped in the reaction vessel containing azeotropically dried CsHCO3 and 18-C-6 dissolved in dry dimethylformamide. The [11C]cyanide was reacted with (S)-tert-butyl-2-((tert-butoxycarbonyl)amino)-4-iodobutanoate at 90 °C for 8 min to obtain the corresponding [11C]cyano derivative which was purified on HPLC using semi-preparative column. The resultant intermediate was then deprotected/hydrolyzed with trifluoroacetic acid and sulfuric acid at 90-95 °C. Results: The average radiochemical yield of [11C]L-glutamine starting from [11C]CO2 was 12.8 + 5.2 % decay corrected to start of synthesis (n = 4). The average radiochemical purity was > 96 % (n = 4). Conclusion: The synthesis of [11C]L-glutamine was successfully accomplished starting from a commercially available starting material on an automated synthesis unit. Further optimization of the yield is in progress.