Radiosynthesis of PET radiotracer as a prodrug for imaging group II metabotropic glutamate receptors in vivo.
Group II metabotropic glutamate receptors (mGluRs) have been implicated in a variety of neurological and psychiatric disorders in recent 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-[(11)C]methoxyphenethyl) glycine dimethyl ester ([(11)C]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 [(11)C]CMGDE readily penetrated into the brain and the radiotracer generated from [(11)C]CMGDE had fast reversible binding in the group II mGluRs rich regions including striatum, hippocampus and different cortical areas. Blocking studies with LY341495 showed 20-30% decrease of binding of the radiotracer generated from [(11)C]CMGDE in all brain areas with the highest decrease in the striatum 31.5±3.2%. The results show [(11)C]CMGDE is the first PET tracer that is brain penetrating and can be used to image group II mGluRs in vivo.
Athinoula A. Martinos Biomedical Imaging Center, Massachusetts General Hospital, Harvard Medical School, 149 13th Street, Charlestown, Massachusetts 2129, USA.
Ji-Quan
JQ
Wang
Zhaoda
Z
Zhang
Darshini
D
Kuruppu
Anna-Liisa
AL
Brownell
D000596:Amino Acids / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000378:metabolism; D006624:Hippocampus / Q000000981:diagnostic imaging / Q000378:metabolism; D008297:Male; D049268:Positron-Emission Tomography / Q000379:methods*; D011355:Prodrugs / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D011485:Protein Binding / Q000187:drug effects; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D018094:Receptors, Metabotropic Glutamate / Q000032:analysis*; D014966:Xanthenes / Q000494:pharmacology
D000596:Amino Acids; C114624:LY 341495; D011355:Prodrugs; D019275:Radiopharmaceuticals; D018094:Receptors, Metabotropic Glutamate; D014966:Xanthenes