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 T1 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. Copyright © 2012 John Wiley & Sons, Ltd.

Stimulation‐induced transient changes in neuronal activity, blood flow and N‐acetylaspartate content in rat prefrontal cortex: a chemogenetic fMRS‐BOLD study

“…DMSO crosses the blood brain barrier and can diffuse through cellular membranes (29). A previous study also reported a strong resonance seen at 2.7 ppm and suggested the use of DMSO as a potential contrast agent for brain tumors (30). This solvent is very efficient as a delivery mechanism for CNO, however care must be taken in the spectral analysis to avoid inaccurate results in the metabolites of interest.…”

DCE@urLAB: a dynamic contrast-enhanced MRI pharmacokinetic analysis tool for preclinical data

“…First, a genetically engineered mouse (GEM, S100-v-ErbB; Ink4a-Arf(+/-)), female, age 40 weeks, bearing a Schwannoma (confirmed by histopathological studies carried out by Dr. Martí Pumarola, Murine Pathology Unit, Centre de Biotecnologia Animal i Teràpia Gènica, UAB ). Animals from this colony generally develop oligodendrogliomas [53], although a small percentage of animals can develop other tumour types [54]. The second model studied was a mouse bearing a stereotactically-induced GL261 glioblastoma, described elsewhere [55,56], age 20 weeks.…”

Development of a transplantable glioma tumour model from genetically engineered mice: MRI/MRS/MRSI characterisation

“…SV spectra were acquired at short and long echo time. Tumour-bearing mice were also studied by PE-MRSI with DMSO [21] and/ or with glucose under mild hypothermia [22,23]. Bloodbrain barrier (BBB) integrity was evaluated with gadoterate meglumine (DOTAREM, Guerbet, Roissy, F rance) using contrast-enhanced (CE) T 1W images.…”

“…c Color-coded intensity map representing the relative DMSO signal (as described in [21]) detected at 66 min after its i.p. administration.…”

“…Single voxel (SV) MRS measures the average metabolic information of a tumour [16,17], whereas multivoxel acquisition MRSI provides spatially resolved metabolic information [18][19][20], which may be superimposed to anatomical acquisitions. Additionally, our group has developed MRSI-based molecular imaging techniques, perturbing the spectral pattern (Perturbation Enhanced Magnetic Resonance Spectroscopic Imaging, PE-MRSI) by injecting different substances, such as dimethyl sulfoxide (DMSO) and glucose [21][22][23], to increase the dynamic range for in vivo preclinical brain tumour characterization. from "A" group (six from fresh and seven from tumour frozen in liquid N 2 for 6 months, groups B and C respectively).…”