Brain Imaging of Serotonin Transporters in the Brain

Healthy, Serotonin Transporter

Neuroreceptors, PET Measurements, Kinetic Analysis, Test/Retest, Healthy Volunteer, HV

Serotonin is a chemical involved in the regulation of emotions, anxiety, sleep, stress, and other body functions. The purpose of this study is to use brain imaging technology to study how serotonin works in the brain. The serotonin transporter (SERT) regulates the release of sertonin throughout the body. Until recently, radioactive chemicals called tracers were not suitable for viewing SERT activity. However, a newly developed tracer called \[11C\]DASB can be used with positron emission tomography (PET) imaging to view the parts of the brain that use serotonin. Participants in this study will be screened with medical and psychiatric examinations, an electrocardiogram (EKG), and blood and urine tests. This study comprises two parts. During Part 1, participants will undergo a whole-body PET scan. During Part 2, participants will undergo a magnetic resonance imaging (MRI) scan of the brain. At the next study visit, participants will have one or two PET head scans. If not is not possible to perform both scans on the same day, an additional visit will be scheduled for the second PET scan.

The serotonin transporter (SERT) modulates the activity of the central serotonergic system and SERT is also the primary target of the widely prescribed specific serotonin reuptake inhibitors. Until recently, suitable radioligands for in vivo imaging of SERT have not been available. However, a recently developed PET radioligand, \[11C\]DASB, appears suitable for quantifying SERT in humans. In the two protocols that have been approved by the CSRP for submission to the IRB, we planned to use \[11C\]DASB PET to study the pathophysiology of SERT in Parkinson's disease and OCD. This protocol was created to address criticisms raised by the NIH RDRC committee and the external scientific review. 1. The NIH RDRC (Radioactive Drug Research Committee) review of this protocol asked that we obtain human biodistribution data to confirm the expected low levels of radiation exposure, based upon our prior studies in monkeys. 2. To address one of the criticisms raised by the CSRP review, namely 1) to quantify SERT binding parameters with \[11C\]DASB in up to 10 normal subjects and 2) to determine the reliability and reproducibility of SERT binding parameter measurements by performing a second retest \[11C\]DASB PET study in the same subjects, because such data are not available for this radioligand. PET scanning will be performed with an intravenous injection of 20 mCi of \[11C\]DASB for 2 h, during which multiple arterial blood samples will also be obtained. The reproducibility of SERT binding parameters will be assessed by calculating the variability as well as the intraclass correlation coefficient between test/retest measurements. We expect that 1) we can accurately quantify SERT binding parameters using \[11C\]DASB PET imaging and 2) \[11C\]DASB PET measurements of SERT binding will be reliable and reproducible.

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