Abstract

BackgroundDopamine 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).MethodsTwenty-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 (BPND) quantification and specific uptake value ratios (SUVR).ResultsPET 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 BPND (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 BPND 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 BPND in the SN (R = 0.816, p < 0.001). Olfaction and mean putamen DAT availability was correlated using both FE-PE2I BPND and FP-CIT SUR (R ≥ 0.616, p < 0.001).ConclusionDAT imaging with FE-PE2I PET yields excellent basic diagnostic differentiation in early-stage PS, at least as good as FP-CIT SPECT.

Highlights

  • Dopamine transporter (DAT) imaging may be of diagnostic value in patients with clinically suspected parkinsonian disease

  • The binding of FP-CIT in the midbrain is to the serotonin transporter, not to the dopamine transporter, whereas FE-PE2I is selective for the DAT

  • Analysis of the entire group of healthy control subjects (HC) showed a significant age correlation with FP-CIT specific uptake ratio (SUR), FE-PE2I Binding potential relative to non-displaceable binding (BPND), and specific uptake value ratios (SUVR) in the caudate, putamen, and whole striatum (Table 2). This age-related correlation was driven by the female HC, since no significant age correlation with DAT activity was evident in men

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Summary

Introduction

Dopamine transporter (DAT) imaging may be of diagnostic value in patients with clinically suspected parkinsonian disease. The spatial and temporal resolution in PET is superior compared to SPECT, and in contrast to conventional DAT SPECT imaging, in vivo visualization and quantification of DAT in extra-striatal regions, such as the substantia nigra (SN) [6, 7], is feasible with FE-PE2I. This is due to the high affinity (KD = 12 nM) [8] and superior selectivity for DAT over the serotonin transporter (SERT), a ratio which is found to be 29.4 for PE2I [9] and 2.78 for FP-CIT [10]. The secondary objectives were to measure the intraclass correlation coefficient between FE-PE2I and FP-CIT outcome measures, to measure the correlation between DAT availability and clinical measures in PS patients, and to examine the usefulness of the quantification of DAT availability in the SN

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