Modifications to the TRACERlab FXF-N for Improved HPLC in the Manufacture of [18F]FLT
Objective: To modify an automated radiochemistry system to facilitate better aseptic technique and chromatographic reproducibility.
Background: The increasing demand for non-pharmacopoeial PET radiopharmaceuticals (e.g. 3’-deoxy-3’-[18F]fluorothymidine, ([18F]FLT)) has caused a proliferation in the number and variety of automated radiochemistry systems worldwide incorporating High Performance Liquid Chromatography (HPLC). The challenges posed with such equipment include aseptic technique and chromatographic reproducibility.
Equipment: Modified TRACERlab FXF-N (GE Medical Systems) with HPLC column heater (Phenomenex) and eluent delivery from PVC bags necessitating vacuum degassing.
Method: HPLC eluents for [18F]FLT purification and column washing were prepared aseptically in PVC bags. A sample was stored for 3 months then analysed for phthalate leaching. Injections of FLT standard were made with the column held at different temperatures and the retention time (tR) of FLT monitored. Batches of [18F]FLT were synthesised using the procedure of Machulla H et. al. (2000) with the HPLC column held at a constant temperature and the chromatographic reproducibility monitored.
Results: Phthalates were not detected. The tR of FLT decreases with an increase in column temperature (0.7 minutes/10°C). Chromatographic reproducibility was not significantly improved by temperature control however other factors such as the undesirable injection of air may have contributed.
Conclusion: Conversion to PVC bags had no negative impact and allowed easier operation with minimised risk of microbial contamination due to improved asepsis. Although column heating did not significantly improve chromatographic reproducibility, it was shown to reduce the tR of FLT. Reduced tR dictates shorter manufacturing time and therefore may help in increasing [18F]FLT yield.