Dopamine transporter (DAT)

The dopamine transporter sits on the axon terminals of presynaptic nigrostriatal dopaminergic neurons, which project from the substantia nigra to the striatum (caudate and putamen), and terminates dopaminergic signalling by taking dopamine back into the neuron after release. Because DAT density on the neuron surface tracks the number of intact nigrostriatal terminals, loss of DAT signal on imaging is a marker of neurodegeneration rather than a direct marker of disease-specific pathology.

Ioflupane I-123 (DaTscan/DATSCAN), a radioiodinated cocaine analogue, binds reversibly to DAT (Ki approximately 0.62 nM) and is imaged by SPECT 3-6 hours after injection, concentrating in the striatum in proportion to transporter density. It is FDA- and EMA-approved as an adjunct for striatal DAT visualisation in adults with suspected parkinsonian syndromes and suspected dementia with Lewy bodies, chiefly to help distinguish essential tremor (normal DAT scan) from Parkinsonian syndromes (reduced striatal DAT), and probable dementia with Lewy bodies from Alzheimer's disease.

As a target, DAT's strength is a clean anatomical readout (striatal uptake) that reliably separates presynaptic neurodegeneration from tremor of other causes. Its main limitation is lack of specificity between the parkinsonian syndromes themselves: DaTscan cannot distinguish idiopathic Parkinson's disease from multiple system atrophy or progressive supranuclear palsy, since all three cause nigrostriatal terminal loss. A range of common drugs (stimulants, some antidepressants, benztropine) bind DAT with high affinity and can interfere with image interpretation, so they typically need to be stopped before scanning.