Automated synthesis of the 16α-[18F]fluoroestradiol ([18F]FES): minimization of precursor amount and resulting benefits

Abstract

Abstract The 16α-[18F]Fluoroestradiol ([18F]FES) is an established PET radiotracer for estrogen positive (ER+) breast cancer. Although the radiosynthesis is well-described, the majority of the published methods suffer from modest or irreproducible yields and time-intensive purification procedures. In view of the considerable clinical applications, development of a more efficient and faster synthesis of [18F]FES still remains a task of a significant practical importance. [18F]FES was produced by a direct nucleophilic radiofluorination of 3-O-methoxymethyl-16,17-O-sulfuryl-16-epiestriol (MMSE), followed by acidic hydrolysis using HCl/CH3CN. [18F]Fluoride retained on a QMA carb cartridge (46 mg) was eluted by solution of 1.2 mg of tetrabutylammonium tosylate (TBAOTs) in EtOH. After fluorination reaction (0.3 mg MMSE, 1 ml of CH3CN/100 °C, 5 min) [18F]FES was isolated by single-cartridge SPE purification using OASIS WAX 3cc, elution accomplished with aqueous ethanol of different concentrations. On а GE TRACERlab FX N Pro automated module [18F]FES (formulated in normal saline with 5% EtOH) was obtained in 33 ± 3% yield (n = 5, non-decay corrected) within 32 min. Reduction of precursor amount, exclusion of azeotropic drying step and simplification of purification make the suggested method readily adaptable to various automated synthesizers and offers significant cost decrease.