Dual-tracer [¹⁸F]-AV133 and [¹⁸F]-FDG PET/MR multiparametric characterization of Parkinson's disease motor subtypes

Two major motor subtypes are widely recognized in Parkinson's disease (PD): tremor-dominant (TD) subtype and the postural instability-gait difficulty (PIGD) subtype. These distinct clinical phenotypes imply divergent underlying neural mechanisms. This study aimed to investigate the neural correlates of TD and PIGD subtypes using multiparametric analysis with hybrid positron emission tomography/magnetic resonance (PET/MR) and two tracers: [¹⁸F]-fluoropropyl-(+)-dihydrotetrabenazine ([¹⁸F]-AV133) and [¹⁸F]-fluorodeoxyglucose ([¹⁸F]-FDG).

A total of 42 patients with PD (22 TD, 20 PIGD) and 27 healthy controls (HCs) were enrolled. Analysis of variance (ANOVA) and post hoc tests were performed to compare presynaptic dopaminergic function, cerebral glucose metabolism, and gray matter volume (GMV) across groups. Correlation analyses further explored relationships between imaging metrics and Movement Disorder Society-Unified Parkinson's Disease Rating Scale Part III (MDS-UPDRS-III) scores. Receiver operating characteristic (ROC) curves were plotted.

Relative to TD-PD patients, PIGD-PD patients showed significantly lower [¹⁸F]-AV133 binding in the bilateral putamen (contralateral anterior putamen: 1.72±0.33 vs. 2.05±0.56, P=0.033; ipsilateral anterior putamen: 1.57±0.38 vs. 1.82±0.40, P=0.044; contralateral posterior putamen: 1.69±0.40 vs. 1.43±0.17, P=0.011; ipsilateral posterior putamen: 1.37±0.14 vs. 1.55±0.33, P=0.030), with more symmetric dopaminergic impairment in the posterior putamen (0.09±0.11 vs. 0.19±0.17, P=0.025). PIGD-PD also exhibited reduced [¹⁸F]-FDG uptake in the lateral/medial prefrontal cortices (P=0.008 and 0.019), putamen (P<0.001), thalamus (P<0.001), pons (P<0.001), and cerebellum (P<0.001). Reduced GMV was noted in the bilateral cerebellum [(lobule IX, lobule IV/V) right lobule IX: P=0.035, left lobule IX: P=0.044, right lobule IV/V: P<0.001, left lobule IV/V: P<0.001], orbital superior frontal gyrus (right: P=0.007, left: P=0.003), postcentral gyrus (right: P=0.025, left: P<0.001), right cerebellar lobule VIII (P=0.048), left cerebellar lobule VIIb (P<0.001), left inferior temporal gyrus (P<0.001), and right thalamus (P=0.005). For PIGD-PD patients, correlation analyses revealed that bilateral putaminal [¹⁸F]-AV133 binding, prefrontal/putaminal [¹⁸F]-FDG uptake, and GMV in the orbital superior frontal gyrus, middle temporal gyrus, and cerebellum were significantly negatively correlated with UPDRS-III scores (r ranging from -0.833 to 0.607, all P<0.05). Multimodal integration achieved excellent discrimination [area under the curve (AUC) =0.923].

TD-PD and PIGD-PD exhibit distinct patterns of presynaptic dopaminergic dysfunction, cerebral hypometabolism, and gray matter atrophy. These neuroimaging differences may partially account for the divergent clinical manifestations between the two motor subtypes, Multimodal integration achieved excellent discrimination.