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DOI: 10.1055/s-0041-1726749
Impact of TSPO polymorphism on [18F]GE-180binding in healthy and pseudoreference tissue of neurooncological and neurodegenerative disorders
Ziel/Aim The 18kDa translocator protein (TSPO) is an established biomarker of microglial activity and known to be overexpressed on cancer cells. TSPO-PET tracers (e.g. 11C-PBR28) are sensitive to a single nucleotid polymorphism (rs6971) resulting in low (LAB), medium (MAB) and high (HAB) affinity binders. In this study, we evaluate the impact of rs6971 on the in vivo [18F]GE-180 signal in healthy controls and in potential pseudoreference tissue for studies of neurooncological and neurodegenerative diseases.
Methodik/Methods Healthy controls (HC,n = 22) and 95 subjects with disease [glioma (n = 34), 4R-tauopathies (4RT,n = 33), Alzheimer’s disease (AD,n = 28)] underwent TSPO genotyping. PET scans were performed after administration of 189 ± 12 MBq [18F]GE-180, and 60–80 min summation images were used for assessment of standardized uptake values (SUV) using a manually drawn region of interest (ROI) in the fronto-parietal hemisphere (HC, glioma) and a cerebellar ROI (HC, 4RT, AD). TSPO-PET SUVs were compared between LAB, MAB and HAB in groups of HC, glioma, 4RT and AD. Second, TSPO-PET SUVs were compared between patients and HC within their rs6971 group.
Ergebnisse/Results Genotyping revealed n = 24 LABs (7 controls, 6 gliomas, 6 4RT, 5 AD). Age- and sex-matched MABs (n = 38; 10 controls, 14 gliomas, 8 4RT, 6 AD) and HABs (n = 50; 5 controls, 14 gliomas, 21 4RT, 15 AD) were included. LABs had lower [18F]GE-180 binding when compared to MABs and HABs, but no difference was observed between MABs and HABs (SUVmean fronto-parietal of HC: LAB 0.35, MAB 0.44, HAB 0.45; LAB/MAB p = 0.02, LAB/HAB p = 0.02, MAB/HAB p = 0.73). Within each rs6971 group, fronto-parietal and cerebellar binding was comparable between disease groups and HC.
Schlussfolgerungen/Conclusions TSPO binding status affects [18F]GE-180 quantification, revealing lower SUV in controls/patients with LAB when compared to MAB/HAB. Fronto-parietal and cerebellar ROI in patients with glioma and neurodegenerative diseases indicate indifferent uptake when compared to controls within their rs6971 groups, underpinning their potential as pseudoreference regions.
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Publikationsverlauf
Artikel online veröffentlicht:
08. April 2021
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