Simultaneous synthesis of O-(2'-(¹⁸F) fluoroethyltyrosine and (¹⁸F) fluoromisonidazole using solid phase extraction method

At present scenario, positron emission tomography (PET) radiopharmaceuticals were synthesized with a complete dedicated synthesis for each production starting from cyclotron irradiation till end of synthesis. Simultaneous production of multiple radiopharmaceuticals would of great advantage as a fast and economical process. As an effort to achieve this, O-(2'-(¹⁸F) fluoroethyltyrosine ((¹⁸F)FET) and (¹⁸F) fluoromisonidazole )(¹⁸F) FMISO), chosen based on their polarity difference, were synthesized simultaneously. (¹⁸F)FET is an analog of L-tyrosine, used as brain tumor imaging agent. Fluoromisonidazole ((¹⁸F)FMISO) is a tumor hypoxia imaging agent. Radiolabeling precursors were obtained from ABX, Germany. All other chemicals were purchased locally. ¹⁸F-fluoride production and radiosynthesis were performed using GE PETtrace cyclotron and GE TRACERlab module (configured for 2-¹⁸F-fluorodeoxyglucose production), respectively. (¹⁸F) radiofluorination was carried out using dry (¹⁸F) tetrabutylammonium fluoride. Reaction parameters were fine-tuned for optimal radiolabeling. The reaction mixture was purified using neutral alumina. The column was washed with 10% ethanolic-water. (¹⁸F)FMISO was eluted with 5 mL of 10% ethanolic water, followed by (¹⁸F) FET by eluting column with water for injection (WFI) from the column. The difference in polarity of both the radiopharmaceuticals makes it viable to separate in a single synthesis run. (¹⁸F)FMISO being more nonpolar is eluted first in 10% ethanol, followed by (¹⁸F) FET using WFI. (¹⁸F)FET and (¹⁸F)FMISO were synthesized with >95% radiochemical and >90% enantiomeric purity with a reliable yield of 10% each. (¹⁸F)FET and (¹⁸F)FMISO were successfully synthesized simultaneously using solid-phase extraction purification. Thus, the process is reliable, fast, and economical. (author)