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

Abstract

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). 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 3T MRI scanner after sequential administration of ALA and FAC. The relaxivity and QSM analysis were performed on the images. The intra-cellular iron deposition was significantly higher in the glioma cells with sequential treatment of ALA and FAC for 6h 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 ± 5s-1 for R2', and 0.1 ± 0.02ppm 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). Sequential administration of ALA and iron supplements increases the iron deposition in glioblastoma cells, enabling clinical 3T MRI to detect GBM using R2' or QSM.