Brain Imaging of Serotonin Transporters in the Brain

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.

• 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.
• 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.

Inclusion criteria

WHOLE BODY IMAGING

Diagnosis: Healthy

Ages: 18-50 years

Exclusion criteria

WHOLE BODY IMAGING

History of psychiatric disease, substance dependence or traumatic brain injury, severe systemic disease, poor vision or hearing.

History of substance abuse within 6 months

Abnormal laboratory tests, including HIV test

Any prior participation in other research protocols involving radiation exposure within the past year

Prior participation in other research protocols within the past year such that a radiation exposure together with the present study would exceed the annual limits

Pregnancy and Breast Feeding

Positive HIV test

Inclusion criteria

PART 2 KINETIC

Age: 18-50 y

Male or female

Consent given

Exclusion criteria

PART 2 KINETIC

DSM-IV Axis I diagnostic criteria such as history of, or current diagnosis ADHD, mood/anxiety disorder, alcohol or psychoactive substance abuse/dependence. All subjects must meet none of the Axis I diagnoses.

Psychotropic medication or other drugs that may cross the blood brain barrier. Drug free period must be greater than 4 weeks (antidepressants and benzodiazepine) and greater than 6 weeks (fluoxetine, antipsychotics, anticonvulsants).

Pregnancy or breastfeeding

Abnormal MRI other than minor atrophy

Abnormal laboratory tests, including HIV test

Claustrophobia

Pregnancy or breast feeding. Women with child bearing potential will a pregnancy test to exclude pregnancy

Prior participation in other research protocols within the past year such that a radiation exposure together with the present study would exceed the annual limits. Limits: A total effective dose or 5.0 rem in a year.

Any condition that increases risk for MRI (e.g., pacemaker, metallic foreign body in the eye, etc.)

Traumatic brain injury, severe systemic disease, poor vision or hearing

Major medical conditions or neurological disorders

Single radial and ulnar arterial circulation. This will be determined during physical examination (A simple wrist compression test)

Individuals who recently donated blood.

Unable to lay on one's back for PET/MRI scans. PET and MRI scans take approximately 2 and 1 hours, respectively.

Novacaine allergy - yes - Local anesthetic used for insertion of arterial and venous catheters.

Positive HIV test