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

The Need &Technology Description
Glucose and its analogues 2-deoxy-D-glucose (2DG) and 2- fluoro-deoxy-D-glucose (FDG) are known to be taken up preferentially by cancer cells, a phenomenon known as the “Warburg effect".
Prof. Gil Navon from Tel Aviv University was able to demonstrate that a non- metabolized glucose analogue named 3-oxy-methyl-D-glucose (3OMG) uptake by tumors provide a higher and prolonged CEST MRI signal , than native (α-D-glucose) glucose thereby providing a cheap, widely available, more comprehensive, non-invasive alternative to nuclear medicine techniques currently used for cancer assessment.
Data Summary
The current efficacy data generated by Prof. Navon utilizing 4T1 mammary orthotropic model suggests that:

• 3OMG lowest effective dose in mice (by oral administration) was defined as ~600mg/kg
  providing a CEST signal of 4% while D-glucose (PO) provides only 1% CEST effect at
  doses of 380-1000 mg.
• The equivalent human oral dose(cancelation made based on ration between mice and human surface area) is about 3.5gr per 70 kg subject (Figure 1)

The glucoCEST MRI signal disappear after an hour while the 3OMG signal is stable one hour
after administration (Figure 2)
Figure 2: Kinetics of 3OMG vs. D-glucose CEST MRI kinetics in 4T1 mammary
orthotropic model (PO administration)

Based on a side by side experiment in 6 animal the 3OMG CEST MRI technology was found
as sensitive as was found with the FDG PET/CT method. Significant 3OMG uptake was seen in
the primary tumor, urinary bladder and in organs suspected to be lung metastasis providing a
clear validation of the 3OMG CEST technique.
Figure 3: Side by Side signal of 3OMG CEST MRI vs. FDG PET/CT (in the same mice
bearing 4T1 cells)

Ongoing work: Characterization of 3OMG signal in mice bearing human mammary tumors, biodistribution of 3OMG, non-GLP tox study with 3OMG, development of additional glucose analogues as reagents for CEST MRI (information will be available under confidentiality agreement
Patents

PCT application No. PCT/IL2015/050327 was filed on March 26, 2015

Project manager

Rona Samler
VP, BD Physical Science, Medical Device, Chemistry

Project researchers

Gil Navon
T.A.U Tel Aviv University, Exact Sciences
School of Chemistry

Ilan Tsarfaty
T.A.U Tel Aviv University, Medicine-Sackler Faculty
Clinical Microbiology and Immunology