Automated synthesis of 11C-acetoacetic acid, a key alternate brain fuel to glucose

An automated, one-pot radio-synthesis module for the routine preparation of 1-[11C]acetoacetic acid has been developed. The enolate anion of acetone was reacted with [11C]CO2 in tetrahydrofuran (THF), followed by hydrolysis and purification by ion-exchange chromatography. The total synthesis time was 18 min and radiochemical yield was 34% after decay correction. HPLC analysis showed ⩽3% impurities while residual THF (⩽200 ppm) and ethanol (⩽500 ppm) were well under the tolerable limits for human studies.