Discovery of [¹¹C]MK-8056: A Selective PET Imaging Agent for the Study of mGluR₂ Negative Allosteric Modulators

Modification of potent, selective metabotropic glutamate receptor 2 negative allosteric modulator (mGluR₂ NAM) led to a series of analogues with excellent binding affinity, lipophilicity, and suitable physicochemical properties for a PET tracer with convenient chemical handles for incorporation of a ¹¹C or ¹⁸F radiolabel. [¹¹C]MK-8056 was synthesized and evaluated in vivo and demonstrated appropriate affinity, selectivity, and physicochemical properties to be used as a positron emission tomography tracer for mGluR₂.