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 (SUV_mean 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.

Publikationsverlauf

Artikel online veröffentlicht:
08. April 2021