Minimizing the production of extraneous unlabelled ethyl iodide in the nuclear interface carbon-11 methyl iodide solid phase synthesis box

Abstract

1915

Objectives: We use the Nuclear Interface solid phase synthesis box, which uses triphenylphosphonium di-iodide absorbed on alumina for the conversion of C-11 methanol to methyl iodide, for the production of C-11 choline. The final product is analyzed by HPLC on a Surfactant R column with 1.4 mM methane sulphonic acid mobile phase to separate the products and a conductivity detector. In addition to the choline, which was detected both on the radioactivity and conductivity detectors, a second non-radioactive peak with similar chromatographic characteristics to choline was consistently detected, although in somewhat variable amounts. This product was identified as ethyl choline by HPLC/MS, i.e. one of the methyl groups of choline had been replaced by an ethyl group. This product could not be detected in the starting material, deanol. Clearly an unlabelled ethylating agent, ethyl iodide, was being produced in the methyl iodide synthesis. A series of experiments have been performed in order to identify the source of this ethyl iodide and minimize or eliminate its production.

Methods: All runs where analyzed by HPLC as above. Runs where performed with the iodinating reagent at furnace temperatures of 180°C and 165°C (reagent temperatures of 162°C and 145°C respectively) and with the triphenylphosphoium di-iodide contained in PEEK (as supplied by the manufacturer) and Teflon holders. In addition runs where performed in which either THF or mono-butyl glycol ether (used to liberate the C-11 methanol from the LAH) where absent.

Results: Ethyl choline was formed in all of the runs regardless of the conditions. However the amount detected could be decreased significantly. The smallest amounts where formed with the furnace temperature of 165°C and the triphenylphosponium di-iodide in a Teflon container. Under these conditions the peak associated with ethyl choline on the conductivity detector was < 20% of the size of the choline peak but it was always formed. The amount formed in a PEEK container was significantly greater than in a Teflon one.

Conclusions: There are multiple sources of unlabeled ethyl iodide in the Nuclear Interface solid phase synthesis box. The PEEK containers, supplied by the manufacturer, are one of these sources.