Drug: [18F]SP203
N/A

Metabotropic glutamate receptors are G-protein coupled receptors that respond to glutamate by activating proteins inside nerve cells that affect cell metabolism, thereby fine-tuning the signals sent between cells to maintain balance in neuronal activity. Metabotropic Glutamate receptors (mGluR5) are Group I receptors localized post-synaptically and found in several regions of the brain including the striatum, hippocampus, amygdala, and cortex.

Activation of mGluR5 stimulates phospholipase C, resulting in phosphoinositide hydrolysis and increase of intracellular Ca(2+) levels. Several potent antagonists for mGluR5 have been developed, including 6-methyl-2-(phenylethynyl)pyridine (MPEP) and 3-[(2-methyl-1,3-thiazol-4yl)ethynyl] pyridine (MTEP) however, no simple derivatives of MPEP or MTEP had proven to be useful for in vivo imaging.

In the present protocol, we will use a new PET ligand [18F]SP203 for two reasons: Phase 1.) we will perform kinetic brain imaging to quantify mGluR5 binding parameters in brain and determine the reliability and reproducibility of these measures in 15 healthy controls Phase 2.) if the tracer is proved successful in phase 1 we plan to estimate radiation-absorbed doses of [18F]SP203 in healthy human subjects by performing whole body imaging.

Successful development of a PET ligand to image mGluR5 will have a strong impact on clinical management of brain disorders with disruptions in glutamatergic transmission such as schizophrenia, anxiety, and neurodegenerative disorders including Alzheimer's and Parkinson's disease.