PET Imaging of Dopamine in Healthy Study Participants
Condition: Healthy
Study type: Interventional
Phase: Phase 2

Summary: 
      The purpose of this study is to measure molecules on or in cells that interact with a
      chemical in the nervous system, called dopamine. Investigators will obtain two kinds of
      images of the brain-a position emission tomography (PET) scan and a magnetic resonance
      imaging (MRI) scan.

      Thirty-eight participants aged 18 to 45 will be enrolled in this study. They must have no
      history of medical or psychiatric illness, including substance abuse. Participants will have
      four appointments at NIH. On the first visit, they will undergo a physical exam, a medical
      history, and lab tests. The second and third visits will involve PET scans and the fourth
      visit will involve an MRI scan.

      Participants will be compensated up to $430 for their involvement in this study.
    

Detailed description: 
      Abnormalities of dopaminergic function have been implicated in a number of neurological and
      psychiatric illnesses, including Parkinson's disease, schizophrenia, and psychostimulant
      dependence syndromes. Functional imaging with positron emission tomography (PET) and single
      photon emission computed tomography (SPECT) have demonstrated the feasibility of in vivo
      measurement of the distribution and the density of dopamine (DA) D1 and D2 receptors in
      humans. Besides simple measurement of receptor density, it has been shown that the
      competition between endogenous neurotransmitters and radiolabeled tracers might provide a
      tool to estimate extracellular levels of neurotransmitters. However, most of those studies
      have been confined to the striatum. In this protocol using a PET tracer (18F)fallypride, we
      will estimate both stimulant-induced DA release and baseline DA levels in the striatum and
      extrastriatal regions by comparing baseline scans and those after d-amphetamine or
      alpha-methyl-para-tryosine (AMPT) adminstration. In addition, to explore genetic factors that
      determine synaptic DA levels, allelic variations of two genes that regulate DA levels,
      catechol-O-methyltransferase and dopamine transporter, will be studied.

      A recent study showed that oral administration of d-amphetamine induced displacement of (11C)
      raclopride in a similar way as the commonly used method of i.v. administration. The current
      protocol will be performed in two steps. First, the method of d-amphetamine administration
      will be determined by studying effects of oral d-amphetamine on the binding of (18F)
      fallypride binding. If oral administration effectively displaces the radioligand binding,
      this method will be applied in the subsequent study of examining effects of each of
      d-amphetamine and AMPT in individual subjects.

      If this study successfully detects the influence of DA levels on (18F)fallypride binding, the
      same design will be applied to the studies of patients with psychiatric and neurological
      disorders.
    

Intervention name(s): (18F)fallypride
Intervention type(s): Drug
Intervention MeSH terms: Fallypride
Primary purpose: Treatment
Keywords: Thalamus; Cerebral Cortices; Quantification; Reproducibility; Dopamine Release; (18F) Fallypride; D-Amphetamine; Alpha-Methyl-Para-Tyrosine (AMPT); PET; Dopamine D2 Receptor; Healthy Volunteer; HV