Synthesis and evaluation in monkey of [¹⁸F]4-Fluoro- N -methyl- N -(4-(6-(methylamino)pyrimidin-4-yl)thiazol-2-yl)benzamide ([ ¹⁸F]FIMX): A promising radioligand for PET imaging of brain metabotropic glutamate receptor 1 (mGluR1)

We sought to develop a PET radioligand that would be useful for imaging human brain metabotropic subtype 1 receptors (mGluR1) in neuropsychiatric disorders and in drug development. 4-Fluoro-N-methyl-N-(4-(6-(methylamino) pyrimidin-4-yl)thiazol-2-yl)benzamide (FIMX, 11) was identified as having favorable properties for development as a PET radioligand. We developed a method for preparing [¹⁸F]11 in useful radiochemical yield and in high specific activity from [¹⁸F]fluoride ion and an N-Boc-protected (phenyl)aryliodonium salt precursor (15). In baseline experiments in rhesus monkey, [¹⁸F]11 gave high brain radioactivity uptake, reflecting the expected distribution of mGluR1 with notably high uptake in cerebellum, which became 47% lower by 120 min after radioligand injection. Pharmacological challenges demonstrated that a very high proportion of the radioactivity in monkey brain was bound specifically and reversibly to mGluR1. [¹⁸F]11 is concluded to be an effective PET radioligand for imaging mGluR1 in monkey brain and therefore merits further evaluation in human subjects.