Dopamine Transporter Imaging, Current Status of a Potential Biomarker: A Comprehensive Review

Abstract

A major goal of current clinical research in Parkinson’s disease (PD) is the validation and standardization of biomarkers enabling early diagnosis, predicting outcomes, understanding PD pathophysiology, and demonstrating target engagement in clinical trials. Molecular imaging with specific dopamine-related tracers offers a practical indirect imaging biomarker of PD, serving as a powerful tool to assess the status of presynaptic nigrostriatal terminals. In this review we provide an update on the dopamine transporter (DAT) imaging in PD and translate recent findings to potentially valuable clinical practice applications. The role of DAT imaging as diagnostic, preclinical and predictive biomarker is discussed, especially in view of recent evidence questioning the incontrovertible correlation between striatal DAT binding and nigral cell or axon counts.

FMR1 deletion in rats induces hyperactivity with no changes in striatal dopamine transporter availability

“…Over the years, techniques as SPECT/PET have been employed enabling imaging of the dopaminergic system in different psychiatric and neurological disorders. Such methods are often based on the assessment of DAT density as a marker for dopaminergic neuron integrity 55,[74][75][76] . Generally, a radiolabel such as 123 I-FP-CIT (DaTSCAN) is used since it is able to bind with high affinity to the presynaptic DAT located on axon terminals in the striatum.…”

“…Generally, a radiolabel such as 123 I-FP-CIT (DaTSCAN) is used since it is able to bind with high affinity to the presynaptic DAT located on axon terminals in the striatum. In the clinical practice, SPECT with 123 I-FP-CIT can be reported as normal or abnormal through the semi-quantitative measurement of the 123 I-FP-CIT signal uptake in the DAT 55 . Therefore, imaging with specific DA-related tracers represents a valuable tool to evaluate the status of presynaptic nigrostriatal terminals.…”

“…Then, the animals were anesthetized using isoflurane (IsoFlo, Zoetis, UK) at a concentration of 3% for induction and 2% for maintenance. In vivo DAT binding was measured using Methyl (3S,4S,5R)-8-(3-fluoropropyl)-3-(4-iodophenyl)-8-azabicyclo[3.2.1] octane-4-carboxylate([ 123 I]FP-CIT, DaTSCAN ® ) as radioligand, since it is widely used to assess the pre-synaptic striatal uptake in the basal ganglia of the rat brain [52][53][54][55] . A dose of 37 ± 4 MBq in 1,25 ml DaTSCAN (GE Healthcare, DE) was administered into the lateral tail vein.…”

Freezing of Gait as a Complication of Pallidal Deep Brain Stimulation in DYT‐KMT2B Patients with Evidence of Striatonigral Degeneration

“…Many dystonia-parkinsonism disorders are associated with reduced striatal dopamine due to degeneration of substantia nigra pars compacta neurons. 5 Our finding of bilateral short putamen on DaTscan is suggestive of striatal dopaminergic denervation in DYT-KMT2B. Contrary to levodopa-induced dyskinesia and wearing-off phenomena in Parkinson's disease (PD), the pattern of striatal dopamine depletion does not seem to affect the risk of FOG in PD.…”

Molecular Imaging in Nanomedical Research 2.0

“…Dopamine-related tracers are a powerful tool used to assess the status of presynaptic nigrostriatal terminals in the brain; Palermo and co-workers [ 7 ] illustrate the use of positron emission tomography and single-photon emission tomography imaging with specific dopamine-related tracers as an indirect imaging biomarker of Parkinson’s disease, and carefully discuss the actual diagnostic and prognostic significance of this imaging approach.…”