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

Int J Mol Sci. 2020 Oct 14;21(20):7598. doi: 10.3390/ijms21207598.

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.

Keywords: IDH1 mutation; MGMT promoter methylation; Primary brain tumors; [18F]FDOPA; nuclear medicine; positron emission tomography; radiopharmaceuticals.

MeSH terms

  • Adult
  • Brain Neoplasms / diagnostic imaging
  • Brain Neoplasms / genetics*
  • DNA Methylation*
  • DNA Modification Methylases / genetics*
  • DNA Repair Enzymes / genetics*
  • Dihydroxyphenylalanine / analogs & derivatives
  • Female
  • Glioma / diagnostic imaging
  • Glioma / genetics*
  • Humans
  • Isocitrate Dehydrogenase / genetics*
  • Male
  • Middle Aged
  • Mutation*
  • Positron Emission Tomography Computed Tomography*
  • Promoter Regions, Genetic
  • Radiopharmaceuticals
  • Tumor Suppressor Proteins / genetics*

Substances

  • Radiopharmaceuticals
  • Tumor Suppressor Proteins
  • fluorodopa F 18
  • Dihydroxyphenylalanine
  • Isocitrate Dehydrogenase
  • IDH1 protein, human
  • DNA Modification Methylases
  • MGMT protein, human
  • DNA Repair Enzymes