The radiotracer [123I]I-FP-CIT binds preferentially to the dopamine transporter expressed at the plasma membrane of nigrostriatal dopaminergic neurons: a new concept

Dopamine transporter (DAT) tracers like [123I]I-FP-CIT are frequently used in routine practice to support the diagnosis in patients suffering from clinically uncertain parkinsonian syndromes as well as in scientific studies. The DAT is expressed not only at the plasma membrane of dopaminergic neurons, but is also trafficking within the cytoplasm. It has been well documented that the striatal [123I]I-FP-CIT binding is lower in disorders neuropathologically characterized by DAT loss induced by degeneration of nigrostriatal dopaminergic neurons (e.g., Parkinson’s disease). In addition, in studies in subjects without dopaminergic degeneration it has been suggested that subtle lower striatal binding can be induced by down-regulation of the DAT. However, theoretically, down-regulation can only be measured if [123I]I-FP-CIT binds predominantly to the DAT expressed at the plasma membrane, but not due to binding to the internalized DAT. We therefore looked into the literature to find support or opposition for this postulate. In this brief narrative review, we found indirect evidence that tracers like [123I]I-FP-CIT binds predominantly to the DAT expressed on plasma membrane of nigrostriatal dopaminergic neurons.