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

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 R 2 ’ 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 C 6 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 R 2 ’, 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 R 2 ’, 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 R 2 ’ or QSM.