Stability Evaluation of 18F-FDG at High Radioactive Concentrations

Abstract

The objective of our study was to determine the concentration of ethanol, a known radiolytic stabilizer, needed to maintain stability for 12 h at an (18)F-FDG concentration of 19.7-22.6 GBq/mL (533-610 mCi/mL) at the end of synthesis (EOS). (18)F(-) was formed by the (18)O(p, n)(18)F reaction using 16.5-MeV protons on a cyclotron. (18)F-FDG was synthesized using a synthesis platform. The final product was formulated in 15 mL of phosphate buffer. The synthesis took 22 min, delivering up to 336.7 GBq (9.1 Ci) of (18)F-FDG at the EOS. A series of 9 runs, 19.7-22.6 GBq/mL (533-610 mCi/mL), was completed. Three runs were doped with 0.1% ethanol, 3 with 0.2% ethanol, and 3 with no ethanol added. The radiochemical purity (RCP) was tested at about 1-h increments over a 12-h period. RCP was found by radio-thin-layer chromatography using aluminum-backed silica gel plates, acetonitrile, and water 90:10. An (18)F-FDG standard of 1 mg/mL was used to confirm radiochemical identity. The chromatography plates were analyzed on a radio-thin-layer chromatograph using a β-detector. Residual solvents were also tested using gas chromatography with flame ionization detection and a capillary column. Other quality control measurements performed were pH and appearance. The 3 runs doped with 0.1% ethanol failed RCP after 5 h. The 3 runs using an ethanol concentration of 0.2% maintained stability through 12 h beyond the EOS. For these 3 runs, the radiolytic impurities were relatively constant at 6.1% ± 0.7% after 3 h. The runs using no ethanol failed RCP at 1 h. The pH varied between 5.3 and 6.1. Visual inspection was always clear and particulate-free. For the runs with 0.2% and 0.1% ethanol, the residual solvents were 0.21% ± 0.02% and 0.10% ± 0.02%, respectively. Regardless of ethanol concentration, chemical purity and identity passed quality control measurements. With the addition of 0.2% ethanol, (18)F-FDG (19.7-22.6 GBq/mL [533-610 mCi/mL]) kept stability through 12 h beyond the EOS. Each run passed stability parameters related to radiolysis-that is, radiochemical identity and RCP, chemical purity and identity, appearance, pH, and residual solvents.