Dopamine imaging is a critical tool in the evaluation of movement disorders, such as Parkinson’s disease (PD) and other neurodegenerative conditions. Two of the primary imaging modalities used to assess the integrity of the dopaminergic system are Single Photon Emission Computed Tomography (SPECT) with the DaTscan radiotracer and Positron Emission Tomography (PET) with tracers targeting the vesicular monoamine transporter type 2 (VMAT2). 

Nerve terminal illustrating the radiotracers used in the study of the dopaminergic system in PD. The dopamine transporter (DAT) is labeled by [123I]FP-CIT (DaTscan SPECT) and VMAT2 (vesicular monoamine transporter type 2) is labeled by [18F]DTBZ.

DaTscan ([123I] ioflupane) is a radiopharmaceutical that binds to the dopamine transporter (DAT) in presynaptic neurons, allowing visualization of dopaminergic nerve terminals in the striatum. This method is particularly useful to diagnose a Parkinsonian syndrome (such as Parkinson’s disease and multiple system atrophy) by differentiating it from other diseases with similar symptoms but without dopaminergic neuron loss, such as essential tremor and other non-degenerative conditions. DaTscan (also referred to as DAT SPECT in this presentation) is widely available and has been clinically validated, but it has limitations, including lower spatial resolution compared to PET imaging. 

VMAT2 PET imaging utilizes radiotracers, such as [18F]DTBZ (florbenazine) or [11C]DTBZ (dihydrotetrabenazine), which bind to VMAT2, a transporter responsible for packaging dopamine into presynaptic vesicles. Unlike DAT SPECT, which reflects dopamine transporter density, VMAT2 PET provides a more direct assessment of presynaptic dopamine storage and function. VMAT2 imaging has demonstrated high sensitivity and specificity for detecting dopaminergic neurodegeneration and may provide more detailed insights into disease progression. 

While DAT SPECT is a well-established and readily available clinical tool, VMAT2 PET imaging provides superior spatial resolution and potentially more accurate assessment of dopamine system integrity. However, PET imaging is less accessible due to the need for specialized facilities and short-lived radiotracers. 

Understanding the strengths and limitations of both imaging techniques is crucial for selecting the most appropriate diagnostic tool in movement disorder evaluation. More information on the various dopamine imaging techniques can be found in our Resource - [18F]DOPA PET in Parkinson's Disease Clinical Trials.

In this Presentation, we explore the natural history changes in dopaminergic terminals, measured by DAT SPECT and VMAT2 PET imaging, in individuals with Parkinson’s disease, using data from the Parkinson's Progression Markers Initiative (PPMI) study, and determine sample sizes required to observe therapeutic effect in those imaging modalities in a PD clinical trial.