Rapid 'on-column' preparation of hydrogen [C-11]cyanide from [C-11]methyl iodide via [C-11]formaldehyde

Hydrogen [C-11]cyanide ([C-11]HCN) is a versatile C-11-labelling agent for the production of C-11-labelled compounds used for positron emission tomography (PET). However, the traditional method for [C-11]HCN production requires a dedicated infrastructure, limiting accessibility to [C-11]HCN. Herein, we report a simple and efficient [C-11]HCN production method that can be easily implemented in C-11 production facilities. The immediate production of [C-11]HCN was achieved by passing gaseous [C-11]methyl iodide ([C-11]CH3I) through a small two-layered reaction column. The first layer contained an N-oxide and a sulfoxide for conversion of [C-11]CH3I to [C-11]formaldehyde ([C-11]CH2O). The [C-11]CH2O produced was subsequently converted to [C-11]HCN in a second layer containing hydroxylamine-O-sulfonic acid. The yield of [C-11]HCN produced by the current method was comparable to that of [C-11]HCN produced by the traditional method. The use of oxymatrine and diphenyl sulfoxide for [C-11]CH2O production prevented deterioration of the molar activity of [C-11]HCN. Using this method, compounds labelled with [C-11]HCN are now made easily accessible for PET synthesis applications using readily available labware, without the need for the 'traditional' dedicated cyanide synthesis infrastructure.