The metabotropic glutamate subtype five (mGluR5) receptor is a protein found in the brain and is the target for the excitatory chemical messenger glutimate. The purpose of this protocol is to measure mGluR5 receptors in the brain using positron emission tomography (PET) and a research drug called [18F]SP203.

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.

• Healthy
• Glutamate Receptor
• mGlur5 Protein
• Excitatory Amino Acid Receptors
• Drug Kinetics
• PET Scan

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• INCLUSION CRITERIA:

Healthy control subjects aged 18-65 years, with history/physical exam, ECG, and laboratory tests within one year of the PET scan within normal limits.

EXCLUSION CRITERIA:

1. Current psychiatric illness, substance abuse or severe systemic disease based on history and physical exam.
2. Laboratory tests with clinically significant abnormalities.
3. Prior participation in other research protocols or clinical care in the last year such that radiation exposure would exceed the annual limits.
4. Pregnancy and breast feeding.
5. Claustrophobia. (part 1 only)
6. Presence of ferromagnetic metal in the body or heart pacemaker. (part 1 only)
7. Positive HIV test.
8. Consumed alcohol within 48 hours before the PET scan.