Dopaminergic Imaging in Parkinsonian Syndromes

Parkinsonian syndromes encompass a spectrum of neurodegenerative disorders characterised by progressive loss of dopaminergic neurons in the nigrostriatal pathway. Dopaminergic imaging, principally with single-photon emission computed tomography (SPECT) and positron emission tomography (PET), provides in vivo insight into presynaptic dopamine transporter (DAT) density, postsynaptic receptor availability and dopamine synthesis capacity. Radiotracers such as [123I]FP-CIT for DAT-SPECT and [18F]FDOPA for PET target distinct facets of the dopaminergic system, offering complementary information on neuronal integrity. Quantitative metrics—including specific binding ratios, asymmetry indices and kinetic parameters—support differential diagnosis of idiopathic Parkinson’s disease (PD), atypical parkinsonian disorders such as multiple system atrophy (MSA) and progressive supranuclear palsy (PSP), and enable monitoring of disease progression. Technological advances in scanner hardware, tracer synthesis and automated image processing have enhanced sensitivity for early and subclinical nigrostriatal dysfunction, facilitating earlier diagnosis, stratified therapeutic decisions and enrichment of clinical trials with objective biomarkers.

Research from Nature Portfolio

Innovations in dual-phase DAT imaging have improved differential diagnosis across parkinsonian phenotypes. A dual-phase 18F-FP-CIT PET protocol, combining early perfusion-like scans with delayed measurements of DAT binding, achieved over 95 percent concordance with clinical diagnoses for PD, MSA and PSP, reducing reliance on multiple imaging modalities. Meanwhile, analysis of binding laterality on DAT-SPECT has shown that asymmetry of specific binding ratios in early-stage PD differs markedly from PSP, reflecting disease-specific nigrostriatal degeneration patterns and enhancing diagnostic discrimination in unilateral presentations.

Dopaminergic Imaging in Parkinsonian Syndromes publication trend

The graph below shows the total number of articles in dopaminergic imaging in parkinsonian syndromes across all publications each year (not limited to Nature Index journals).

Technical terms

Dopamine transporter (DAT): Membrane protein that clears dopamine from the synaptic cleft, imaged to assess presynaptic neuronal integrity.

Specific binding ratio (SBR): Quantitative value comparing tracer uptake in a target region with reference tissue, indicating transporter or receptor availability.

[18F]FDOPA PET: PET technique using fluorinated DOPA to measure presynaptic dopamine synthesis by tracking aromatic l-amino acid decarboxylase activity.

[123I]FP-CIT SPECT: SPECT method employing an iodine-labelled tropane derivative to visualise DAT distribution in the striatum.

Nigrostriatal pathway: Dopaminergic neural tract linking the substantia nigra to the striatum, crucial for modulation of voluntary movement.

Asymmetry index: Metric expressing the difference in tracer uptake between left and right hemispheres, highlighting unilateral degeneration.

Differential diagnosis: Clinical process of distinguishing among parkinsonian syndromes based on imaging and symptomatology.

Radiotracer molar activity: Radioactivity per mole of tracer compound, affecting image contrast and quantification accuracy.

References

1. A systematic review of the potential effects of medications and drugs of abuse on dopamine transporter imaging using [123I]I-FP-CIT SPECT in routine practice. European Journal of Nuclear Medicine and Molecular Imaging (2023).
2. Update on the Role of [18F]FDOPA PET/CT. Seminars in Nuclear Medicine (2024).
3. Diagnostic accuracy of dual-phase 18F-FP-CIT PET imaging for detection and differential diagnosis of Parkinsonism. Scientific Reports (2021).
4. Laterality of specific binding ratios on DAT-SPECT for differential diagnosis of degenerative parkinsonian syndromes. Scientific Reports (2020).
5. Decoding the dopamine transporter imaging for the differential diagnosis of parkinsonism using deep learning. European Journal of Nuclear Medicine and Molecular Imaging (2022).