title: Dimethyl sulfoxide (DMSO) as a potential contrast agent for brain tumors.
abstract: Dimethyl sulfoxide (DMSO) is commonly used in preclinical studies of animal models of high-grade glioma as a solvent for chemotherapeutic agents. A strong DMSO signal was detected by single-voxel MRS in the brain of three C57BL/6 control mice during a pilot study of DMSO tolerance after intragastric administration. This led us to investigate the accumulation and wash-out kinetics of DMSO in both normal brain parenchyma (n=3 control mice) by single-voxel MRS, and in 12 GL261 glioblastomas (GBMs) by single-voxel MRS (n=3) and MRSI (n=9). DMSO accumulated differently in each tissue type, reaching its highest concentration in tumors: 6.18 ± 0.85 µmol/g water, 1.5-fold higher than in control mouse brain (p<0.05). A faster wash-out was detected in normal brain parenchyma with respect to GBM tissue: half-lives of 2.06 ± 0.58 and 4.57 ± 1.15 h, respectively. MRSI maps of time-course DMSO changes revealed clear hotspots of differential spatial accumulation in GL261 tumors. Additional MRSI studies with four mice bearing oligodendrogliomas (ODs) revealed similar results as in GBM tumors. The lack of T(1) contrast enhancement post-gadolinium (gadopentetate dimeglumine, Gd-DTPA) in control mouse brain and mice with ODs suggested that DMSO was fully able to cross the intact blood-brain barrier in both normal brain parenchyma and in low-grade tumors. Our results indicate a potential role for DMSO as a contrast agent for brain tumor detection, even in those tumors 'invisible' to standard gadolinium-enhanced MRI, and possibly for monitoring heterogeneities associated with progression or with therapeutic response.
authors: Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Unitat de Biociències, Edifici C, Cerdanyola del Vallès, Spain.
authors: T
authors: T
authors: Delgado-Goñi
authors: J
authors: J
authors: Martín-Sitjar
authors: R V
authors: RV
authors: Simões
authors: M
authors: M
authors: Acosta
authors: S
authors: S
authors: Lope-Piedrafita
authors: C
authors: C
authors: Arús
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology*; D003287:Contrast Media / Q000737:chemistry / Q000493:pharmacokinetics; D004121:Dimethyl Sulfoxide / Q000737:chemistry / Q000493:pharmacokinetics*; D005240:Feasibility Studies; D005260:Female; D005909:Glioblastoma / Q000378:metabolism* / Q000473:pathology*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008657:Metabolic Clearance Rate; D051379:Mice; D008810:Mice, Inbred C57BL; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014018:Tissue Distribution
chemical_list: D003287:Contrast Media; D004121:Dimethyl Sulfoxide