Anita Ebrahimpour1, Fatemeh Tirgar2, Behnam Hajipour-Verdom3, Ardeshir Abbasi4, Mahmoudreza Hadjighassem5, Parviz Abdolmaleki3, Saereh Hosseindoost5, Seyed Amir Hossein Javadi6, Hassan Hashemi7, Abbas Rahimi Foroushani8, Nader Riyahi Alam9,10, Mehdi Khoobi11,12. 1. Department of Medical Physics and Biomedical Engineering, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran. 2. Department of Neuroscience and Addiction Studies, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran. 3. Department of Biophysics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran. 4. Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran. 5. Brain and Spinal Cord Injury Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran. 6. Department of Neurosurgery, Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran. 7. Department of Radiology, Faculty of Medicine, Tehran University of Medical Sciences (TUMS), Tehran, Iran. 8. Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran. 9. Department of Medical Physics and Biomedical Engineering, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran. riahinad@sina.tums.ac.ir. 10. Concordia University, PERFORM Center, Montreal, QC, Canada. riahinad@sina.tums.ac.ir. 11. Biomaterials Group, The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran. m-khoobi@tums.ac.ir. 12. Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran. m-khoobi@tums.ac.ir.
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.
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.
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