Translocator protein PET imaging in temporal lobe epilepsy: A reliable test-retest study using asymmetry index.

Autor: Mahmud M; Department of Brain Sciences, Imperial College London, London, United Kingdom., Wade C; Department of Brain Sciences, Imperial College London, London, United Kingdom., Jawad S; Department of Brain Sciences, Imperial College London, London, United Kingdom., Hadi Z; Department of Brain Sciences, Imperial College London, London, United Kingdom., Otoul C; Clinical Imaging Translational, UCB Pharma SA, Brussels, Belgium., Kaminski RM; Department of Medicinal Chemistry, Faculty of Pharmacy, Jagiellonian University Medical College, Krakow, Poland., Muglia P; GRIN Therapeutics, Brussels, Belgium., Kadiu I; Clinical Imaging Translational, UCB Pharma SA, Brussels, Belgium., Rabiner E; Translational Applications, Invicro LLC, London, United Kingdom., Maguire P; Clinical Imaging Translational, UCB Pharma SA, Brussels, Belgium., Owen DR; Department of Brain Sciences, Imperial College London, London, United Kingdom., Johnson MR; Department of Brain Sciences, Imperial College London, London, United Kingdom.
Jazyk: angličtina
Zdroj: Frontiers in neuroimaging [Front Neuroimaging] 2023 Apr 28; Vol. 2, pp. 1142463. Date of Electronic Publication: 2023 Apr 28 (Print Publication: 2023).
DOI: 10.3389/fnimg.2023.1142463
Abstrakt: Objective: Translocator protein (TSPO) targeting positron emission tomography (PET) imaging radioligands have potential utility in epilepsy to assess the efficacy of novel therapeutics for targeting neuroinflammation. However, previous studies in healthy volunteers have indicated limited test-retest reliability of TSPO ligands. Here, we examine test-retest measures using TSPO PET imaging in subjects with epilepsy and healthy controls, to explore whether this biomarker can be used as an endpoint in clinical trials for epilepsy.
Methods: Five subjects with epilepsy and confirmed mesial temporal lobe sclerosis (mean age 36 years, 3 men) were scanned twice-on average 8 weeks apart-using a second generation TSPO targeting radioligand, [ 11 C]PBR28. We evaluated the test-retest reliability of the volume of distribution and derived hemispheric asymmetry index of [ 11 C]PBR28 binding in these subjects and compared the results with 8 (mean age 45, 6 men) previously studied healthy volunteers.
Results: The mean (± SD) of the volume of distribution ( V T ), of all subjects, in patients living with epilepsy for both test and retest scans on all regions of interest (ROI) is 4.49 ± 1.54 vs. 5.89 ± 1.23 in healthy volunteers. The bias between test and retest in an asymmetry index as a percentage was small (-1.5%), and reliability is demonstrated here with Bland-Altman Plots (test mean 1.062, retest mean 2.56). In subjects with epilepsy, V T of [ 11 C]PBR28 is higher in the (ipsilateral) hippocampal region where sclerosis is present than in the contralateral region.
Conclusion: When using TSPO PET in patients with epilepsy with hippocampal sclerosis (HS), an inter-hemispheric asymmetry index in the hippocampus is a measure with good test-retest reliability. We provide estimates of test-retest variability that may be useful for estimating power where group change in V T represents the clinical outcome.
Competing Interests: PMa, CO, RMK, and IK have served as paid employees for UCB Pharma SA. ER was employed by Invicro LLC. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The authors declare that this study received funding from UCB Pharma SA. The funder had the following involvement in the study: Provided scientific review of the protocol and results and participated in the writing of this publication.
(Copyright © 2023 Mahmud, Wade, Jawad, Hadi, Otoul, Kaminski, Muglia, Kadiu, Rabiner, Maguire, Owen and Johnson.)
Databáze: MEDLINE
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