Electrochemical radiolabeling of COX-2 inhibitors: potential PET agents for imaging of inflammation.

Objectives Develop a method for radiolabeling metabolically stable COX-2 inhibitors and evaluate resulting constructs for PET imaging of inflammation. Several attempts at developing ¹⁸F labeled COX-2 imaging agents were reported in the literature¹. All of them relied on classic SN2 reactions of organic precursors with radioactive ¹⁸F-fluoride. Due to the limitations of existing strategies, fluoride could only be attached to the positions vulnerable to the in vivo degradation.

Methods Recently we reported a method for radiolabeling of aromatic compounds via electrochemical fluorination on platinum electrodes. Building up on this method we developed an automated set up incorporating fluoride preparation, electrochemistry and purification subsystems. The central part of this apparatus is an electrochemical cell comprised of a gas-tight teflon reactor equipped with two platinum electrodes and a silver wire as a reference electrode. A previously described² COX-2 inhibitor based on substituted arylpyrazole was used as a precursor for radiolabeling. Sulfonamide group was protected with two Boc-protecting groups.

Results We have developed a precursor suitable for electrochemical radiolabeling (1) and utilized it to produce ¹⁸F labeled COX-2 inhibitor using an automated set up. Molecule ¹⁸F-1 was isolated in a radiochemically pure form and formulated in the matrix suitable for animal injection.

Conclusions Electrochemcial radiofluorination is a method suitable for radiolabeling of heteroaromatic compounds, including pyrazole-based COX-2 inhibitors. In vitro validation and in vivo evaluation of the resulting agents is underway.

Research Support UCLA Scholars in Oncologic Molecular Imaging program (NIH grant R25T CA098010)