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. 2025 Jun 2;4(2):e70123.
doi: 10.1002/pcn5.70123. eCollection 2025 Jun.

[18F]FE-PE2I PET is a diagnostic tool in dementia with Lewy bodies

Andrea Sturchio  1   2 , Jonas E Svensson  3   4 , Mikael Tiger  3 , Anton Forsberg Morén  3 , Andrea Varrone  3 , Per Svenningsson  1 , Yoshiro Okubo  5 , Amane Tateno  5
Affiliations

[18F]FE-PE2I PET is a diagnostic tool in dementia with Lewy bodies

Andrea Sturchio et al. PCN Rep. .

Abstract

Aim: Dementia with Lewy bodies (DLB) is characterized by motor and non-motor symptoms. The degeneration of the dopaminergic pathway is a hallmark of DLB; for this reason, we aimed to study a recent dopamine transporter (DAT) positron emission tomography (PET) radioligand as a diagnostic tool for DLB.

Methods: In this study, we used DAT-PET with the radioligand [18F]FE-PE2I to distinguish DLB subjects from healthy controls (HCs). We also aimed to analyze how DAT binding correlated with clinical features, amyloid load, measured by PET, and cardiac metaiodobenzylguanidine scintigraphy (MIBG).

Results: Binding potential (BP ND) values of [18F]FE-PE2I were higher in HCs versus DLB in striatum (1.82 ± 0.34 vs. 1.15 ± 0.34; p < 0.001; 95% Confidence Interval [CI]: 0.40-0.96), putamen (2.2 ± 0.36 vs. 1.41 ± 0.51; p < 0.001; 95% CI: 0.39-1.17), caudate (1.38 ± 0.30 vs. 0.88 ± 0.20; p < 0.001; 95% CI: 0.28-0.70), and substantia nigra (0.49 ± 0.091 vs. 0.42 ± 0.084; p = 0.0437; 95% CI: 0.003 to 0.14). After adjusting for age, substantia nigra did not differ between DLB and HCs (p: 0.46; 95% CI: -0.049 to 0.11); however, BP ND values between DLB and HC in striatum (p: <0.001; 95% CI: 0.25-0.85), putamen (p: 0.0012; 95% CI: 0.31-1.13), and caudate (p: 0.0027; 95% CI: 0.13-0.55) were still significant. Striatum was the best area to correctly classify DLB subjects versus HC compared to the putamen, caudate, and substantia nigra (area under the curve = 0.95, 0.90, 0.93, and 0.73, respectively; 95 CI: 0.87-1.00, 0.79-1.00, 0.84-1.00, 0.55-0.92, respectively). Subjects with altered MIBG showed lower BP ND compared to subjects with normal MIBG in the putamen.

Conclusion: Our study showed that [18F]FE-PE2I PET represents a potential diagnostic tool with high accuracy in discriminating DLB patients versus HC, which is valuable for clinical practice.

Keywords: [18F]FE‐PE2I; dementia with Lewy bodies; dopamine transporter (DAT) imaging; neurodegeneration; neuroimaging.

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Conflict of interest statement

The authors declare no conflict of interest or other interest that might be perceived to influence the results and/or discussion reported in this paper. Andrea Sturchio is a co‐founder of REGAIN Therapeutics and is a co‐inventor of the patent “Compositions and methods for treatment and/or prophylaxis of proteinopathies.” Andrea Sturchio received payment from Baillie Gifford. Per Svenningsson has received honoraria from Sanofi Genzyme and Shire/Takeda.

Figures

Figure 1
Figure 1
Mean wavelet‐aided parametric images of [18F]FE‐PE2I BP ND in healthy control subjects (left) and subjects with dementia with Lewy bodies (right).
Figure 2
Figure 2
Differences between [18F]FE‐PE2I BP ND values between subjects with dementia with Lewy bodies (DLB) versus healthy controls (HCs) in (a) in the striatum, (b) putamen, (c) caudate, and (d) substantia nigra. BP ND, binding potential. Data are represented as mean ± standard deviation.
Figure 3
Figure 3
Receiver operating characteristic (ROC) curve of [18F]FE‐PE2I BP ND in detecting dementia with Lewy bodies (DLB) subjects in (a) the striatum, (b) putamen, (c) caudate, and (d) substantia nigra. HC, healthy controls; BP ND, binding potential. Data are represented as mean ± standard deviation.
Figure 4
Figure 4
Differences between [18F]FE‐PE2I BP ND values between subjects with dementia with Lewy bodies (DLB) metaiodobenzylguanidine negative (MIBG−) and MIBG positive (MIBG+) in the (a) striatum, (b) putamen, (c) caudate, and (d) substantia nigra. HC, healthy controls; BP ND, binding potential. Data are represented as mean ± standard deviation.
See this image and copyright information in PMC

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