Neutral pH Formulation for 6-[18F]fluoro-ʟ-DOPA With High Radiochemical Stability

Abstract 6-[18F]Fluoro-L-DOPA(FDOPA) has always been generally produced under strong acidic conditions, i.e. as an injectable solution of pH 2~3, due to its low stability at a higher or neutral pH. This necessitates the pre-treatment neutralization of this agent with an injectable NaHCO3 solution. We have developed a neutral pH formulation for [18F]FDOPA using ethanol (EtOH) and phosphate buffer to overcome the radioactive and enantiomeric stability problems at a higher pH. Upon [18F]FDOPA generation by nucleophilic substitution methods, we investigated its radiochemical and enantiomeric purity in accordance with the various pH after 6 hours. After EtOH and three kinds of buffer were added, we further examined this purity at pH 6 ~ 7 after 6 hours. The ascorbic acid did not stabilize the radiochemical purity at the higher pH. A 5% EtOH and PBS buffer matrix produced the best stability for radiochemical and enantiomeric purity at pH 6.5 at the 6 hour time point. This combination maintained a > 95% radiochemical and enantiomeric purity at 6 hours after EOS (end of synthesis). Our new formulation for [18F]FDOPA thus showed a high stability at neutral pH and satisfied QC requirements which was listed in European Pharmacopeia. It has also been approved by the Korean Ministry of Food and Drug Safety.