Positron emission tomography in premotor Parkinson's disease

Functional imaging can be used to detect preclinical evidence of dopamine deficiency in people deemed to be at increased risk of Parkinson's disease (PD) based on genetic or environmental risk, or because they have clinical features such as REM sleep behaviour disorder that may be a harbinger of PD. Positron emission tomography (PET) using [11C]dihydrotetrabenazine to label the vesicular monoamine transporter type 2 (VMAT2), a variety of 11C- or 18F-labeled ligands for the membrane dopamine transporter (DAT), or 6-[18F]fluoro-L-dopa (FD), which assesses uptake and decarboxylation of levodopa as well as vesicular storage of radiolabeled dopamine, can all be used, and all provide comparable, but somewhat different information. DAT binding using either PET or SPECT appears to be the most sensitive marker of dopamine denervation, while FD uptake is subject to compensatory upregulation and its reduction may more closely herald the onset of clinical disease. Alterations in glucose metabolism and in dopamine release also occur in the asymptomatic hemisphere of subjects with unilateral PD. An interesting potential application of PET is the determination of non-dopaminergic abnormalities that correlate with the presence of clinically apparent pre-motor symptoms of PD.