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Detection of tumors and metastases by using CEST-MRI of 3-O-Methylglucose

A method to identify and study the degree of malignancy of a tumor using Chemical Exchange Saturation Transfer (CEST) imaging technique in MRI by applying a glucose-based contrast agent.
A combination of imaging techniques is often necessary to differentiate between cancerous and normal tissues. MRI is an excellent noninvasive modality for the detection of tumors. However, it is not sensitive enough to the degree of the malignancy of the tumors.
Tumor cells preferentially uptake glucose (or its analogs) over normal cells, as they rely on enhanced aerobic glycolysis for their energy supply, which distinguishes them from normal tissue. We have developed and improved the sensitivity of the MRI technology with a new diagnostic tool for in vivo cancer imaging aided by a combination of a contrast agent based on a non-metabolizable glucose analog named 3-O-Methyl-D-glucose (3-OMG) and the Chemical Exchange Saturation Transfer (CEST) imaging technique. Basically, CEST enables imaging of molecules indirectly by transferring their magnetization to water. Conventional MRI is based on measuring the signal of water. The reduction of the water signal following the transfer of saturation from the other molecules gives the "CEST contrast". Attempts to use the natural glucose for imaging of tumors by CEST-MRI were already tested and displayed a serious limitation due to its rapid conversion to lactic acid, which leads to reduced CEST effect and short signal duration. The use of CEST, with the 3-OMG enables the detection of cancer as observed by imaging of 3-OMG uptake and accumulation in tumors.

Generally, current technology used in daily clinical practice is only semi-quantitative, while 3OMG CEST technology will be based on a quantitative analysis of its uptake and accumulation in proliferating cells, that will therefore be more reliable, increasing its specificity for the characterization of malignancy and assessment of response to therapy.
This is an easy, safe and cheap method that can be used on the existing installed MRI base across the world, reducing cost and complexity and improving availability.
3-OMG is excreted unchanged from the body and is considered to devoid of any toxic effects. Because of its properties, 3-OMG has the ability to serve as a biocompatible contrast agent, thus has a potential future clinical applications for molecular imaging.
The non-radioactive, non-invasive imaging of 3-OMG uptake and accumulation through CEST MR imaging will also open up the field of molecular imaging for a multitude of non-cancer diseases.


US 2018/0177898