Development of a new precursor-minimizing base control method and its application for the automated synthesis and SPE...

Bases such as potassium carbonate and potassium bicarbonate (KHCO3 ) are essential for the elution of trapped [(18) F]fluoride from ion exchange cartridges and for the prevention of [(18) F]fluoride adsorption on the silica glass vial during the preparation of radiopharmaceuticals for positron emission tomography imaging. However, these bases promote the chemical decomposition of precursor compounds and the creation of unwanted organic impurities. Thus, the goal of the current study was to develop a new method for synthesizing [(18) F]fluoride-labeled radiopharmaceuticals (e.g., [(18) F]fluoromisonizadole ([(18) F]FMISO)) that permits the fine control of base concentrations while minimizing adverse events. Non-decay-corrected radiochemical yields of 25.1 ± 5.0% and 13.3 ± 5.1% (n = 3) were achieved after solid-phase extraction purification using automatic synthesis with GE TRACERlab MX and KHCO3 at concentrations of 14.1 and 33.0 µmol, respectively, and 1 mg of precursor (1-(2'-nitro-1'-imidazolyl)-2-O-tetra-hydropyranyl-3-O-toluenesulfonyl propanediol (NITTP)). The newly developed synthesis protocol with fine base control and low precursor content permits high radiochemical yields with minimal impurities.