Self-immolative Magnetic Resonance Imaging Contrast Agents Sensitive to beta-glucuronidase

INVENTION: Northwestern researchers have created a Magnetic Resonance Imaging contrast agent providing a non-invasive diagnostic for necrotic tumors. The contrast agent is highly sensitive to the enzyme beta-glucuronidase, present in high extracellular levels near necrotic tumors due to an immune response. This novel agent is significantly more sensitive than current 19F MRI agents for this purpose.

ADVANTAGES: A unique type of MRI contrast agent affording specific, rapid and enhanced sensitivity to necrotic tumors versus known 19F indicators.

SUMMARY: In 2003, there were approximately 10,000 MRI units worldwide, and an estimated 75 million scans performed. As the use of MRI continues to grow advances in image enhancement and specificity promise new and improved applications. Contrast in signal intensity between specific tissues and components can convey critical physiological and metabolic information. The title new contrast agent (CA) responds to the presence of necrotic tumors that exhibit high extracellular levels of the enzyme beta-glucuronidase near necrotic tumors due to an immune response. The CA consists of a beta-glucuronic acid moiety, linker and a macrocycle containing the MRI active paramagnetic gadolium (III) species. Beta-glucuronidase catalyzed hydrolysis of the glycosidic bond initiates release of the MRI agent. The process facilitates an increase in the number of water molecules coordinated to the gadolium (III) complex, which in turn affects the spin-lattice relaxation time of the bulk water and corresponding signal. The CA is the first example of a self-decomposable linker (immolative linker), known to be effective in chemotherapeutic prodrug delivery due to fast enzyme hydrolysis kinetics. The unique agent affords specific, rapid and enhanced sensitivity to necrotic tumors versus known 19F indicators. A synthetic scheme affording a range of compositions and properties has been developed for this new type of contrast agent.

STATUS: A patent application has been filed. Northwestern is interested in commercial development of this technology

Inventor(s): Joseph Duimstra, Thomas Meade

Type of Offer: Licensing

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