Radiosynthesis of PET radiotracer as a prodrug for imaging group II metabotropic glutamate receptors in vivo

摘要

Group II metabotropic glutamate receptors (mGluRs) have been implicated in a variety of neurological and psychiatric disorders in recent pathological studies. As a noninvasive medical imaging technique and a powerful tool in neurological research, positron emission tomography (PET) offers the possibility to visualize and study group II mGluRs in vivo under physiologic and pathologic conditions. We synthesized a PET tracer, (S,S,S)-2-(2-carboxycyclopropyl)-2-(3-[¹¹C]methoxyphenethyl) glycine dimethyl ester ([¹¹C]CMGDE), as a prodrug for group II mGluRs, and studied its preliminary biological properties in Sprague-Dawley rats to visualize group II mGluRs. The microPET studies demonstrated that [¹¹C]CMGDE readily penetrated into the brain and upon entering into brain the radiotracer generated from [¹¹C]CMGDE had fast reversible binding in the group II mGluRs rich regions including striatum, hippocampus and different cortical areas. Blocking studies with showed 20–30% decrease of binding of the radiotracer generated from [¹¹C]CMGDE in all brain areas with the highest decrease in the striatum 31.5 ± 3.2%. The results show [¹¹C]CMGDE is the first PET tracer that is brain penetrating and can be used to image group II mGluRs in vivo.