Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Impact of TSPO Receptor Polymorphism on [18F]GE-180 Binding in Healthy Brain and Pseudo-Reference Regions of Neurooncological and Neurodegenerative Disorders

Version 1 : Received: 19 April 2021 / Approved: 20 April 2021 / Online: 20 April 2021 (13:28:14 CEST)

A peer-reviewed article of this Preprint also exists.

Vettermann, F.J.; Harris, S.; Schmitt, J.; Unterrainer, M.; Lindner, S.; Rauchmann, B.-S.; Palleis, C.; Weidinger, E.; Beyer, L.; Eckenweber, F.; Schuster, S.; Biechele, G.; Ferschmann, C.; Milenkovic, V.M.; Wetzel, C.H.; Rupprecht, R.; Janowitz, D.; Buerger, K.; Perneczky, R.; Höglinger, G.U.; Levin, J.; Haass, C.; Tonn, J.C.; Niyazi, M.; Bartenstein, P.; Albert, N.L.; Brendel, M. Impact of TSPO Receptor Polymorphism on [18F]GE-180 Binding in Healthy Brain and Pseudo-Reference Regions of Neurooncological and Neurodegenerative Disorders. Life 2021, 11, 484. Vettermann, F.J.; Harris, S.; Schmitt, J.; Unterrainer, M.; Lindner, S.; Rauchmann, B.-S.; Palleis, C.; Weidinger, E.; Beyer, L.; Eckenweber, F.; Schuster, S.; Biechele, G.; Ferschmann, C.; Milenkovic, V.M.; Wetzel, C.H.; Rupprecht, R.; Janowitz, D.; Buerger, K.; Perneczky, R.; Höglinger, G.U.; Levin, J.; Haass, C.; Tonn, J.C.; Niyazi, M.; Bartenstein, P.; Albert, N.L.; Brendel, M. Impact of TSPO Receptor Polymorphism on [18F]GE-180 Binding in Healthy Brain and Pseudo-Reference Regions of Neurooncological and Neurodegenerative Disorders. Life 2021, 11, 484.

Journal reference: Life 2021, 11, 484
DOI: 10.3390/life11060484

Abstract

TSPO-PET tracers are sensitive to a single-nucleotide-polymorphism (rs6971-SNP) resulting in low (LAB), medium (MAB) and high (HAB) affinity binders, but the clinical relevance for [18F]GE-180 is still unclear. We evaluate the impact of rs6971-SNP on in vivo [18F]GE-180 binding in healthy brain and in pseudo-reference tissue in neurooncological and neurodegenerative diseases. Standardized uptake values (SUV) of [18F]GE-180-PET were assessed using a manually drawn region of interest in the fronto-parietal and cerebellar hemisphere. SUVs were compared between LAB, MAB and HAB in controls, glioma, 4-repeat tauopathies (4RT) and Alzheimer’s disease (AD) subjects. Second, SUVs were compared between patients and controls within their rs6971-subgroup. After exclusion of patients with prior therapy, n=24 LABs (n=7 controls, n=5 glioma, n=6 4RT, n=6 AD) were analysed. Age- and sex-matched MABs (n=38) and HABs (n=50) were selected. LABs had lower fronto-parietal and cerebellar SUVs when compared to MABs and HABs, but no significant difference was observed between MABs and HABs. Within each rs6971 group no SUV difference between patients and controls was detected in the pseudo-reference tissues. The rs6971-SNP affects [18F]GE-180 quantification, revealing lower binding in LABs when compared to MABs/HABs. Fronto-parietal and cerebellar ROIs were successfully validated as pseudo-reference regions.

Keywords

microglia; neurodegeneration; Alzheimer’s disease; neurooncology; 4R-tauopathies; TSPO-PET

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