Feasible method to remove the residual impurity after [¹¹C]methionine production

Objectives: [¹¹C]Methionine is widely used for tumor imaging as a radiopharmaceutical, i.e., gliomas in neurooncology as well as a supplementary in adenocarcinoma by positron emission tomography (PET) and simple synthetic methods are well established with more efficient, reliable and simple setups. Among them, a solid-phase extraction (SPE) cartridge method is nowadays the most common procedure for highly convenient and efficient production of [¹¹C]methionine. However, it was often contaminated by an additional impurity such as sodium iodide not mentioned in the Eu. Ph. Monograph. and consequently contained in the final injectable solution. We herein describe the further purification method that can be easily removed an impurities in the process of production for [¹¹C]methionine or before.

Methods: Three methods were tried to remove an additional impurity which is generated during [¹¹C]methionine production: i) Cleaning method for the [¹¹C]methyl iodide synthetic loop part in the automatic synthesizer with helium flow and heating (750 ^oC) for 2 hrs, ii) Introduction of an additional NaOH cartridge in the next part of Porapak Q which was trapped [¹¹C]methyl iodide source and iii) Additional installation of anion-exchange resin cartridge before sterile filtration. In order to analyze the change of concentration for sodium iodide according to the three methods, it was evaluated by radio-HPLC under the following conditions: YMC triart-C18 column (3.9 x 250 mm), 10 μL of injection volume taken from each final solution, flow rate of 0.9 mL/min, elution solvent of 0.01 M NaH₂PO₄, UV-220 nm and gamma-ray detector.

Results: The concentration analyzed by HPLC after cleaning of synthetic loop for [¹¹C]methyl iodide synthesis with helium flow and heating was decreased around 37% compared with that of maximum impurity but increased again after re-production. The method for additional introduction of NaOH cartridge showed around 28% of reduction. However, introduction of conventional QMA cartridges (anion-exchange resin) was able to remove up to 95% by controlling the pH of collected solution before sterilization. The produced [¹¹C]methionine after further introduction of anion- exchange resin was suitable to the European Pharmacopoeia standards for quality controls with no change of radiochemical yield.

Conclusions: We can be successively removed the impurity (iodide) generated in the [¹¹C]methionine production process using SPE cartridges as introduction an additional anion-exchange resin cartridge. The developed method expected that it can be well adapted to other [¹¹C]radiopharmaceuticals produced by SPE method.