Molecular imaging of dopamine transporters

Abstract

The dopamine transporter (DAT) is responsible for clearance of dopamine from the synaptic cleft after its release. Imaging DAT availability provides a measure of dopamine terminal function and a method for detecting the striatal dopamine terminal dysfunction present in idiopathic Parkinson’s disease (PD) and atypical neurodegenerative parkinsonian disorders such as multiple system atrophy (MSA), progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD). DAT imaging with positron emission tomography (PET) or single photon emission computed tomography (SPECT) can be used to support or refute a diagnosis of dopamine deficient parkinsonism in cases where this is unclear and rationalise a trial of dopamine replacement agents as therapy. It can also detect subclinical dopaminergic dysfunction when present in subjects at risk for PD such as relatives of patients, susceptibility gene mutation carriers, and subjects with late onset hyposmia or sleep disorders. The presence of normal DAT availability on imaging can help categorise “subjects without evidence of dopamine deficiency” (SWEDDs) who on occasion mimic PD and include dystonic tremors, drug-induced and psychogenic parkinsonism in their ranks. Reduced levels of baseline striatal DAT availability on PET or SPECT scanning, however, should be regarded as supportive rather than diagnostic of dopamine deficient parkinsonism.