PET Imaging of Brain 5-HT(1A) Receptors Using [(11)C](-)-RWAY
Condition: Healthy Volunteers
Study type: Interventional
Phase: Phase 1

Summary: 
      This study will use positron emission tomography (PET) and magnetic resonance imaging (MRI)
      to measure a serotonin receptor subtype in the brain called 5-HT(1A). This receptor is a
      target for drug therapy to treat anxiety and depression. The study will see if a newly
      developed radioligand (radioactive substance used in PET scanning to study the receptor
      systems of the brain) called [(11)C](-)-RWAY is more effective than other radioligands
      currently used in brain receptor research.

      Healthy subjects 18-40 years of age may be eligible for this study. Candidates are screened
      with a physical examination, electrocardiogram, and blood and urine tests.

      Participants undergo PET and MRI scanning as follows:

      PET scan

      PET uses small amounts of a radioactive chemical called a tracer (in this case,
      [(11)C](-)-RWAY) that "labels" active areas of the brain. For the procedure, the subject lies
      on the scanner bed. A special mask is fitted to the subject's head and attached to the bed to
      help keep the head still during the scan so the images will be clear. A brief scan is done
      just before the tracer is injected to provide measures of the brain that will help in the
      precise calculation of information from subsequent scans. Then, the tracer is injected
      through a catheter (plastic tube) placed in the arm and pictures are taken for about 2 hours,
      while the subject lies still on the scanner bed. Subjects return to the clinic for blood and
      urine tests 24 hours after the scan.

      MRI

      The MRI scan is done within 1 year of the PET scan. MRI uses a magnetic field and radio waves
      to produce images of body tissues and organs-in this case, the brain. The subject lies on a
      table that is moved into the scanner (a tube-like device), wearing earplugs to muffle the
      noise of the machine during the scanning process. The space in the scanner is confining and
      may cause some people to be somewhat anxious. An intercom system allows the subject to speak
      with the staff member performing the study at all times during the procedure, and the
      procedure can be stopped at any time.
    

Detailed description: 
      The 5-hydroxytryptamine (serotonin, 5-HT) 5-HT(1A) receptors subtype is a target for drug
      therapy in the treatment of anxiety and depression. Radioligands currently in use with PET
      for studying human brain 5-HT(1A) receptors in clinical research or drug development are
      based on WAY-100635. Though variously effective, they each suffer from one or more drawbacks
      with respect to measuring relative regional receptor densities. These drawbacks include:
      rapid metabolism and very low non-specific binding for [carbonyl-(11)C]WAY-100635;
      defluoridation for [18F]trans-FCWAY. Therefore, we have recently developed [(11)C](-)-RWAY as
      an alternative radioligand for brain 5 HT(1A) receptors. Even though similar to WAY-100635,
      [(11)C](-)-RWAY has a reversed amide linkage. Reversal of the direction of the amide bond may
      confer resistance to amide hydrolysis and make acceptable easy labeling at its O-methoxy
      group. In the present protocol, we plan to perform a kinetic brain imaging study in healthy
      human subjects to measure 5 HT(1A) receptors in brain regions with [(11)C](-)-RWAY.
    

Intervention name(s): [11C] (-)-RWAY
Intervention type(s): Drug
Primary purpose: Treatment
Keywords: Serotonin; Positron Emission Tomograhy; Brain; Neurochemistry; Neurotransmitter; Healthy Volunteer; HV