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

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

In a reaction column, gaseous ¹¹C]methyl iodide was converted to ¹¹C]formaldehyde in a first layer containing N-oxide and then transformed into hydrogen ¹¹C]cyanide in a second layer containing hydroxylamine-O-sulfonic acid within 2 minutes.