MGMT Promoter Methylation and IDH1 Mutations Do Not Affect [18F]FDOPA Uptake in Primary Brain Tumors

Abstract

The aim of our study was to investigate the effects of methylation of O⁶-methylguanine-DNA methyltransferase promoter (MGMTp) and isocitrate dehydrogenase 1 (IDH 1) mutations on amino acid metabolism evaluated with 3,4-dihydroxy-6-[18F]-fluoro-l-phenylalanine ([18F] FDOPA) positron emission tomography/computed tomography (PET/CT). Seventy-two patients with primary brain tumors were enrolled in the study (33 women and 39 men; mean age 44 ± 12 years old). All of them were subjected to PET/CT examination after surgical treatment. Of them, 29 (40.3%) were affected by grade II glioma and 43 (59.7%) by grade III. PET/CT was scored as positive or negative and standardized uptake value ratio (SUVr) was calculated as the ratio between SUVmax of the lesion vs that of the background. Statistical analysis was performed with the Mann–Whitney U test. Methylation of MGMTp was detectable in 61 out of the 72 patients examinated. Mean SUVr in patients without methylation of MGMTp was 1.44 ± 0,38 vs. 1.35 ± 0.48 of patients with methylation (p = 0.15). Data on IDH1 mutations were available for 43 subjects; of them, 31 are IDH-mutant. Mean SUVr was 1.38 ± 0.51 in patients IDH mutant and 1.46 ± 0.56 in patients IDH wild type. MGMTp methylation and IDH1 mutations do not affect [18F] FDOPA uptake in primary brain tumors and therefore cannot be assessed or predicted by radiopharmaceutical uptake parameters.

TERT-Promoter Mutational Status in Glioblastoma – Is There an Association With Amino Acid Uptake on Dynamic 18F-FET PET?

“…Hence, it needs to be evaluated, if further PET-based analyses with the extraction of radiomic features may add value to the conventional image analysis in order to noninvasively identify the TERTp-mutational status. Interestingly, the predictability of key mutations using standard and advanced PET quantification also seems to vary depending on the used radioligands (53)(54)(55)(56)(57).…”

18F-FDOPA PET/CT SUV-Derived Indices and Volumetric Parameters Correlation in Patients with Primary Brain Tumors

“…According to other similar reports from our research group, PET/CT was performed in the 18F-FDOPA group [8,11,12]. For the reconstruction of PET images, we used ordered subset expectation maximization (OSEM) with standard technique with four iterations and 20 subsets of data were acquired in a 3D model in a 256 × 256 matrix for the acquisition of the images.…”

“…According to previous studies of our research group [8,11,12], the occipital region was chosen for SUVmax calculation for the background (SUVmax occ), obtained using a standard VOI of 1.5 cm × 1.5 cm ×1.5 cm, placed on the occipital lobe. The occipital region, that was unaffected in all subjects involved as detectable by both PET/CT and MRI data, has been chosen as background instead of the striatum or the contralateral hemisphere in order to avoid discrepancies due the eventual affection of these cortical regions [8,11,12].…”

“…The recent World Health Organization (WHO) Classification of Tumors of the Central Nervous System (2016) describes primary brain tumors based on histopathologic features and molecular genetic alterations [4]. The possible effects of these characteristics on 18 F-FDOPA uptake in primary brain tumors (PBT) have been studied: for instance, the correlation between 18 F-FDOPA uptake in brain tumor cells and glioma grade has been analyzed by several authors [5,6], with higher uptake of the radiotracer in high-grade gliomas; moreover, the possible effects of molecular-genetic alterations of gliomas on amino-acid metabolism using 18 F-FDOPA PET/computed tomography (CT) has been investigated, showing no significant correlations in the two studies [7,8].…”

“…This paper aims to focus on the SUV max ratio calculation methodology. Since none of the patients examined had PBT in the occipital regions as detectable by both PET/CT and MRI data, this site has been selected for SUVmax calculation for the background, based on previous studies of our research group [8,11,12] in which the occipital region was chosen in order to generate ratios of tumor SUV.…”