Dopamine transporter imaging with [18F]FE-PE2I PET and [123I]FP-CIT SPECT—a clinical comparison

Jakobson Mo et al. EJNMMI Research (2018) 8:100 https://doi.org/10.1186/s13550-018-0450-0 ORIGINAL RESEARCH Open Access Dopamine transporter imaging with [18F]FE-PE2I PET and [123I]FP-CIT SPECT—a clinical comparison Susanna Jakobson Mo1,2* , Jan Axelsson2,3, Lars Jonasson2,4, Anne Larsson2,3, Mattias J. Ögren1,2, Margareta Ögren1, Andrea Varrone5, Linda Eriksson6, David Bäckström6, Sara af Bjerkén4,6, Jan Linder2,6 and Katrine Riklund1,2 Abstract 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 (BPND) 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 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). Conclusion: DAT imaging with FE-PE2I PET yields excellent basic diagnostic differentiation in early-stage PS, at least as good as FP-CIT SPECT. Keywords: Parkinson’s disease, PET, SPECT, Dopamine transporter (DAT), [18F]FE-PE2I * Correspondence: 1 Department of Radiation Sciences, Diagnostic Radiology, Umeå University, Umeå, Sweden 2 Umeå Center for Functional Brain Imaging, Umeå University, Umeå, Sweden Full list of author information is available at the end of the article © The Author(s). 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. Jakobson Mo et al. EJNMMI Research (2018) 8:100 Background Dopamine transporter (DAT) imaging is a key supporting diagnostic examination to distinguish patients with idiopathic parkinsonism (PS) (e.g., Parkinson’s disease, multisystem atrophy, progressive supranuclear palsy, and Lewy body dementia) from patients with Parkinson-like symptoms with preserved dopaminergic function. DAT imaging with the commercially available radiopharmaceutical [123I]FP-CIT ([123I]-ioflupane, DaTSCAN™, GE Healthcare, B.V Eindhoven, NL) SPECT (FP-CIT) is an established method, widely used in both clinical practice and research projects [1]. In recent years, a novel radiopharmaceutical for DAT imaging, [18F]FE-PE2I ([18F]-(E)-N-(3-iodoprop-2-enyl)-2β-carbofluoroethoxy-3β(4′-methyl-phenyl) nortropane) for PET (FE-PE2I), has emerged as a promising alternative, allowing a more selective and detailed DAT visualization and quantification [2, 3]. PET imaging with FE-PE2I permits faster patient throughput due to faster kinetics, allowing for reduced time between injection and imaging, and a shorter static imaging protocol [2, 4]. There is no need for pre- and post-scan administration of thyroid protecting agents when using [18F], and the effective dose is comparable to FP-CIT [5]. Moreover, 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 binding of FP-CIT in the midbrain is to the serotonin transporter, not to the dopamine transporter, whereas FE-PE2I is indeed selective for the DAT. The quantification of the DAT binding in the substantia nigra indicates the availability of the DAT on the cell bodies of the dopaminergic neurons. Therefore, FE-PE2I is a potentially attractive, high-quality PET imaging alternative tool for visualization of presynaptic dopamine integrity both in the striatum and in the SN in research and clinical practice. Despite the potential advantages of FE-PE2I compared to FP-CIT, these two ligands have previously not been directly compared in patients. The aim of this study was to compare the basic diagnostic performance of FE-PE2I and FP-CIT in patients with newly onset parkinsonism, fulfilling the step 1 clinical criteria for an idiopathic parkinsonian syndrome at first visit, and healthy control subjects (HC). In clinical practice, the visual interpretation of DAT imaging is very important; however, quantitative measurements are often also used, whereas in research settings the quantitative assessment is essential. Here, the primary objective was to measure the effect size and accuracy of these two DAT imaging methods in separating early-stage PS patients from control subjects, using Page 2 of 13 clinically relevant quantitative image evaluation methods. 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 a (...truncated)