AI Summary
The text discusses the importance of assessing the in vivo status of the midbrain dopaminergic system in neurodegenerative diseases. It highlights the use of a radiopharmaceutical called FP-CIT, or DATScan, to visualize striatal dopamine transporters. The scan is approved for differentiating essential tremor from neurodegenerative parkinsonian syndromes and for suspected dementia with Lewy bodies. The ability to distinguish Lewy body disease from other causes of cognitive impairment is especially important as potential disease-modifying therapies are developed.
Several neurodegenerative diseases affect the midbrain dopaminergic system. A key component of disease pathogenesis is dysfunction of presynaptic dopamine neurotransmission by the dopamine transporter (DAT). The DAT is a sodium/chloride–dependent transporter responsible for dopamine release and reuptake, thereby maintaining dopaminergic homeostasis in the extracellular environment, which plays a key role in movement, motivation, and striatal plasticity.1 Downregulation of DAT is seen in many neurodegenerative parkinsonian conditions and has therefore become an attractive target for neuroimaging seeking to assess the in vivo status of the midbrain dopaminergic system. N–fluoropropyl-2β-carbomethoxy-3β-(4-[123I] iodophenyl) nortropane (FP-CIT), or ioflupane I-123 for short, is an intravenously delivered radiopharmaceutical that is used to visualize striatal DATs using SPECT imaging, henceforth referred to as the DATScan. First approved by the Food and Drug Administration (FDA) in 2011 for the differentiation of essential tremor from neurodegenerative parkinsonian syndromes, the scan cannot clinically distinguish different forms of parkinsonian syndromes because all cause DAT depletion. More recently, suspected dementia with Lewy bodies was added to the list of FDA-approved indications. Utility of a DATScan in this situation is of specific interest because patients with Lewy body disease (LBD) may present with a cognitive syndrome alone, without clinically evident parkinsonism, and distinguishing this from other neuropathologic causes of cognitive impairment will be important as disease-modifying therapies advance in clinical trials and practice.