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Kaiser, Lena; Holzgreve, Adrien; Quach, Stefanie; Ingrisch, Michael; Unterrainer, Marcus; Dekorsy, Franziska J.; Lindner, Simon; Ruf, Viktoria; Brosch-Lenz, Julia; Delker, Astrid; Böning, Guido; Suchorska, Bogdana; Niyazi, Maximilian; Wetzel, Christian H.; Riemenschneider, Markus J.; Stöcklein, Sophia; Brendel, Matthias; Rupprecht, Rainer; Thon, Niklas; Baumgarten, Louisa von; Tonn, Jörg-Christian; Bartenstein, Peter; Ziegler, Sibylle and Albert, Nathalie L. (2022): Differential Spatial Distribution of TSPO or Amino Acid PET Signal and MRI Contrast Enhancement in Gliomas. In: Cancers, Vol. 14, No. 1

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Simple Summary Radiotracers targeting the translocator protein (TSPO) have recently gained substantial interest, since TSPO is overexpressed in malignant gliomas, where it correlates inversely with patient's survival. The high-affinity TSPO PET ligand [F-18]GE180 was found to depict tumor areas with a remarkably high contrast and has been shown to provide non-invasive information on histological tumor grades. Yet, its significance was questioned with the argument, that the high contrast may solely arise from nonspecific accumulation in tissue supplied by leaky vessels. This study aimed to address this question by providing a detailed evaluation of spatial associations between TSPO and amino acid PET with relative contrast enhancement in T1-weighted MRI. The results show that [F-18]GE180 contrast does not reflect a disrupted blood-brain barrier (BBB) only and that multi-modal imaging generates complementary information, which may better depict spatial heterogeneity of tumor biology and may be used to individualize the therapy for each patient. In this study, dual PET and contrast enhanced MRI were combined to investigate their correlation per voxel in patients at initial diagnosis with suspected glioblastoma. Correlation with contrast enhancement (CE) as an indicator of BBB leakage was further used to evaluate whether PET signal is likely caused by BBB disruption alone, or rather attributable to specific binding after BBB passage. PET images with [F-18]GE180 and the amino acid [F-18]FET were acquired and normalized to healthy background (tumor-to-background ratio, TBR). Contrast enhanced images were normalized voxel by voxel with the pre-contrast T1-weighted MRI to generate relative CE values (rCE). Voxel-wise analysis revealed a high PET signal even within the sub-volumes without detectable CE. No to moderate correlation of rCE with TBR voxel-values and a small overlap as well as a larger distance of the hotspots delineated in rCE and TBR-PET images were detected. In contrast, voxel-wise correlation between both PET modalities was strong for most patients and hotspots showed a moderate overlap and distance. The high PET signal in tumor sub-volumes without CE observed in voxel-wise analysis as well as the discordant hotspots emphasize the specificity of the PET signals and the relevance of combined differential information from dual PET and MRI images.

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