Automated radiochemical synthesis of pharmaceutical grade [¹⁸F]FLT using 3‐N‐Boc‐5′‐O‐dimethoxytrityl‐3′‐O‐nosyl‐thymidine precursor and its Sep‐Pak® purification employing selective elution from reversed phase

Abstract

Pharmaceutical grade 3 0 -deoxy-3 0 -[ 18 F]fluorothymidine [ 18 F]FLT was synthesized using 3-N-Boc-5 0 -O-dimethoxytrityl-3 0 -O-nosyl-thymidine (BOC-Nosyl) precursor, in the general purpose TRACERlab FX modules. Purification of [ 18 F]FLT, via solid phase extraction (SPE) after radiosynthesis, using a combination of different SPE cartridges, yielded satisfactory results, with radiochemical and chemical purity >99%. While the non-decay corrected radiochemical yield (RCY) with 20 mg (24 μmole) of BOC-Nosyl precursor was found to be 6.80 ± 0.16%, the decay corrected radiochemical yield (RCY) was 9.95 ± 0.24%. Residual acetone, acetonitrile, and ethanol levels were found to be 22.97

Automated Optimized Synthesis of [18F]FLT Using Non-Basic Phase-Transfer Catalyst with Reduced Precursor Amount

“…We also observed radioactivity loss in a gaseous form, which was marked as “uncontrolled losses” (entry 9, Table 2 ). Comparable or slightly lower RCY (10%, corrected for decay) for the [ 18 F]FLT has been recently reported [ 22 ] using a similar GE TRACERlab FX automated platform ( Table 1 , entry 5). The authors used 20 mg of I and employed a quite complex purification procedure based on four different types of SPE cartridges.…”

“…As an alternative to HPLC purification, the development of solid-phase extraction (SPE) techniques based on commercially available disposable cartridges has been the focus of radiopharmaceutical research for many radiotracers including [ 18 F]FLT [ 16 , 20 , 21 , 22 ]. The SPE method, in principle, is very simple, fast, reliable, and is easily adaptable to most automated equipment.…”

“…However, in contrast to the HPLC, to achieve a satisfactory chemical purity of the radiotracer through cartridge-based purification is a challenging task, especially considering the formation of potentially toxic side-products such as 2′,3′-didehydro-2′,3′-dideoxythymidine (stavudine) [ 23 ]. To date, several SPE purification procedures for the [ 18 F] FLT have been described [ 16 , 20 , 21 , 22 ]. With 20–25 mg of I typically used, removal of chemical impurities was achieved by means of combining different type of SPE cartridges and intermediate sorption/eluting steps, this, in turn, required more complex automation.…”