Detection of glioblastoma multiforme using quantitative molecular magnetic resonance imaging based on 5-aminolevulinic acid: in vitro and in vivo studies

MAGMA. 2022 Feb;35(1):3-15. doi: 10.1007/s10334-021-00978-1. Epub 2021 Dec 8.

Abstract

Objectives: We demonstrated a novel metabolic method based on sequential administration of 5-aminolevulinic acid (ALA) and iron supplement, and ferric ammonium citrate (FAC), for glioblastoma multiforme (GBM) detection using R2' and quantitative susceptibility mapping (QSM).

Materials and methods: Intra-cellular iron accumulation in glioblastoma cells treated with ALA and/or FAC was measured. Cell phantoms containing glioblastoma cells and Wistar rats bearing C6 glioblastoma were imaged using a 3 T MRI scanner after sequential administration of ALA and FAC. The relaxivity and QSM analysis were performed on the images.

Results: The intra-cellular iron deposition was significantly higher in the glioma cells with sequential treatment of ALA and FAC for 6 h compared to those treated with the controls. The relaxivity and magnetic susceptibility values of the glioblastoma cells and rat brain tumors treated with ALA + FAC (115 ± 5 s-1 for R2', and 0.1 ± 0.02 ppm for magnetic susceptibility) were significantly higher than those treated with the controls (55 ± 18 (FAC), 45 ± 15 (ALA) s-1 for R2', p < 0.05, and 0.03 ± 0.03 (FAC), 0.02 ± 0.02 (ALA) ppm for magnetic susceptibility, p < 0.05).

Discussion: Sequential administration of ALA and iron supplements increases the iron deposition in glioblastoma cells, enabling clinical 3 T MRI to detect GBM using R2' or QSM.

Keywords: 5-Aminolevulinic acid; Ferric ammonium citrate; Glioblastoma multiforme; Intra-cellular iron accumulation; Quantitative susceptibility mapping.

MeSH terms

  • Aminolevulinic Acid
  • Animals
  • Glioblastoma* / diagnostic imaging
  • Iron
  • Magnetic Resonance Imaging / methods
  • Rats
  • Rats, Wistar

Substances

  • Aminolevulinic Acid
  • Iron