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Background: Dopamine transporter (DAT) imaging may be of diagnostic value in patients with clinically suspected parkinsonian disease. The purpose of this study was to compare the diagnostic performance of DAT imaging with positron emission computed tomography (PET), using the recently developed, highly DAT-selective radiopharmaceutical [¹⁸F]FE-PE2I (FE-PE2I), to the commercially available and frequently used method with [¹²³I]FP-CIT (FP-CIT) single-photon emission computed tomography (SPECT) in early-stage idiopathic parkinsonian syndrome (PS).

Methods: Twenty-two patients with a clinical de novo diagnosis of PS and 28 healthy controls (HC) participating in an on-going clinical trial of FE-PE2I were analyzed in this study. Within the trial protocol, participants are clinically reassessed 2 years after inclusion. A commercially available software was used for automatic calculation of FP-CIT-specific uptake ratio (SUR). MRI-based volumes of interest combined with threshold PET segmentation were used for FE-PE2I binding potential relative to non-displaceable binding (BP_ND) quantification and specific uptake value ratios (SUVR).

Results: PET with FE-PE2I revealed significant differences between patients with a clinical de novo diagnosis of PS and healthy controls in striatal DAT availability (p < 0.001), with excellent accuracy of predicting dopaminergic deficit in early-stage PS. The effect sizes were calculated for FE-PE2I BP_ND (Glass’s Δ = 2.95), FE-PE2I SUVR (Glass’s Δ = 2.57), and FP-CIT SUR (Glass’s Δ = 2.29). The intraclass correlation (ICC) between FE-PE2I BP_ND FP-CIT SUR was high in the caudate (ICC = 0.923), putamen (ICC = 0.922), and striatum (ICC = 0.946), p < 0.001. Five of the 22 patients displayed preserved striatal DAT availability in the striatum with both methods. At follow-up, a non-PS clinical diagnosis was confirmed in three of these, while one was clinically diagnosed with corticobasal syndrome. In these patients, FE-PE2I binding was also normal in the substantia nigra (SN), while significantly reduced in the remaining patients. FE-PE2I measurement of the mean DAT availability in the putamen was strongly correlated with BP_ND in the SN (R = 0.816, p < 0.001). Olfaction and mean putamen DAT availability was correlated using both FE-PE2I BP_ND and FP-CIT SUR (R ≥ 0.616, p < 0.001).

Conclusion: DAT imaging with FE-PE2I PET yields excellent basic diagnostic differentiation in early-stage PS, at least as good as FP-CIT SPECT.