Dopaminergic Radiopharmaceutical Imaging in Parkinsonian Syndromes: From Molecular Targets to Clinical Decision-Making

Abstract

Parkinsonian syndromes comprise overlapping neurodegenerative and non-degenerative disorders, making aetiological diagnosis difficult, while existing procedural guidance does not fully integrate tracer-specific biology with clinical decision-making, multimodal strategies, and emerging quantitative and pathology-directed biomarkers. This review synthesises evidence on the molecular targets, radiopharmaceutical characteristics, biological interpretation, and clinical applications of dopaminergic single-photon emission computed tomography (SPECT) and positron emission tomography (PET), focusing on the dopamine transporter (DAT), aromatic L-amino acid decarboxylase (AADC), vesicular monoamine transporter type 2 (VMAT2), dopamine D2/D3 receptors, differential diagnosis, semiquantification, kinetic modelling, and artificial intelligence-assisted interpretation. The evidence confirms that DAT SPECT with [123I]ioflupane ([123I]FP-CIT) remains the most established method for demonstrating or arguing against presynaptic nigrostriatal dysfunction, but an abnormal result cannot establish aetiology, and a normal result can redirect evaluation towards non-degenerative mimics; target-specific PET provides complementary biological information, although availability, standardisation, and prospective validation remain limiting. By additionally integrating genetic and prodromal applications, question-driven multimodal imaging, emerging acquisition approaches, α-synuclein imaging and seed amplification assays, and contemporary biological staging frameworks, this review extends procedural guidance and positions dopaminergic imaging as a targeted functional biomarker selected according to the unresolved clinical question rather than as a stand-alone disease label.