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Radiology. 2014 Sep;272(3):720-30. doi: 10.1148/radiol.14131459. Epub 2014 May 12.

Malignant glioma: MR imaging by using 5-aminolevulinic acid in an animal model.

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From the Departments of Radiology (H.R.C., D.H.K., W.K.M., M.H.H., S.H.C.), Radiation Applied Life Science (H.R.C.), and Neurosurgery (C.K.P.), Seoul National University College of Medicine, 28 Yongon-dong, Chongno-gu, Seoul, 110-744, Korea; Research Institute, National Cancer Center, Gyeonggi-do, Korea (D.K.); Department of Chemistry and Forensic Science, University of Technology, Sydney, Australia (P.D., D.B., D.H.); and Center for Nanoparticle Research, Institute for Basic Science (S.H.C.), and School of Chemical and Biological Engineering (S.H.C.), Seoul National University, Seoul, Korea.



To evaluate the use of 5-aminolevulinic acid (5-ALA) for the noninvasive detection of malignant gliomas by using in vivo magnetic resonance (MR) imaging in a mouse brain tumor model.


The experiments were animal care committee approved. U-87 glioblastoma cells were exposed to 5-ALA (500 ┬Ámol/L) for 6 hours, cells were harvested, and intracellular concentrations of iron, heme, protoporphyrin IX, and ferrochelatase were measured (six in each group). BALB/c nude mice (n = 10) were inoculated with U-87 glioma cells to produce orthotopic brain tumors. T2-weighted imaging was performed 3 weeks after inoculation, and T2* maps were created with a 7-T MR imager before and 24 hours after oral administration of 5-ALA (0.1 mg/g of body weight; n = 6) or normal saline (n = 4). Intratumoral iron concentrations were measured with laser ablation inductively coupled plasma mass spectrometry. For in vitro experiments, differences in the measured data were assessed by using the Mann-Whitney U test with Bonferroni correction. For the in vivo studies, differences in T2* values and iron concentrations of the tumors in the 5-ALA and control groups were assessed by using the Mann-Whitney U test.


The intracellular concentration of heme and iron was increased at both 24 and 48 hours after 5-ALA exposure (P = .004). 5-ALA promoted expression of ferrochelatase in glioblastoma cells at both 24 and 48 hours after 5-ALA exposure compared with that at 1 hour (P = .004). In vivo MR imaging revealed a lower median T2* value in glioblastomas treated with 5-ALA compared with those in control mice (14.0 msec [interquartile range, 13.0-14.5 msec] vs 21.9 msec [interquartile range, 19.6-23.2 msec]; P = .011), and laser ablation inductively coupled plasma mass spectrometry revealed that iron concentrations were increased in glioblastomas from the 5-ALA group.


Administration of 5-ALA increased the intracellular iron concentration of glioblastomas by promoting the synthesis of heme, which is the metabolite of 5-ALA. Because intracellular iron can be detected at MR imaging, 5-ALA may aid in the identification of high-grade foci in gliomas.

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