[Striatal dopamine transporter distribution pattern and its correlation with iron deposition in the substantia nigra pars compacta in Parkinson's disease based on ¹⁸F-FP-CIT PET-MRI]

Objective: To investigate the striatal dopamine transporter (DAT) distribution pattern and its relationship with iron deposition in the substantia nigra pars compacta (SNc) in patients with Parkinson's disease (PD) using integrated ¹⁸F-N-(3-fluoropropyl)-2β-carbomethoxy-3β- Methods: A case-control study. PD patients and sex-and age-matched control group who visited the Department of Nuclear Medicine/PET Center, Huashan Hospital, Fudan University from January 2023 to April 2024 were retrospectively enrolled. Differences in striatal (caudate, putamen) DAT specific binding ratio (SBR) and SNc iron deposition between the two groups were compared using ¹⁸F-FP-CIT PET-MRI. Pearson correlation analysis was used to assess the correlations of striatal DAT-SBR and SNc iron deposition with age, disease duration, Unified Parkinson's Disease Rating Scale Part Ⅲ (UPDRS-Ⅲ) scores, and Mini-Mental State Examination (MMSE) scores were analyzed in the PD group. A non-linear mixed model was used to study the spatiotemporal distribution pattern of striatal DAT-SBR in PD patients and to explore the correlation between striatal DAT-SBR and SNc iron deposition. Results: The PD group consisted of 53 patients (34 males, 19 females) aged (64.5±9.4) years. The control group consisted of 10 subjects (7 males, 3 females) aged (60.2±10.4) years. DAT-SBR in the bilateral caudate (left: 4.50±1.89 vs 7.17±2.29; right: 4.22±1.72 vs 7.03±2.31) and bilateral putamen (left: 4.01±1.80 vs 8.48±2.09; right: 3.60±1.49 vs 8.17±2.12) were significantly lower in the PD group than those in the control group (all P<0.001). SNc iron deposition was significantly higher in the PD group than that in the control group [(96.93±29.94) vs (72.42±8.73)×10^-9, P<0.05]. In the PD group, DAT-SBR in the bilateral caudate and putamen was negatively correlated with age and disease duration (r=-0.535--0.350, all P<0.05), while SNc iron deposition showed no significant correlation with age or disease duration (all P>0.05). After adjusting for age and disease duration, DAT-SBR in the putamen was negatively correlated with UPDRS-Ⅲ scores (r=-0.380, P<0.05), but showed no significant correlation with MMSE scores (P>0.05). The non-linear mixed model results indicated that the decline in DAT-SBR in the caudate and putamen occurs 11.8-17.5 years before clinical onset. After further adjusting for age, disease duration, and UPDRS-Ⅲ scores, DAT-SBR in the bilateral caudate and the posterior part of the right putamen showed negative correlations with SNc iron deposition in the PD group (r=-0.548--0.422, all P<0.05). Conclusion: At the time of clinical diagnosis, striatal DAT is already impaired and shows a negative correlation with SNc iron deposition, revealing a correlation between nigrostriatal pathway damage and DAT impairment in PD patients.