A GI-Specific Contrast Agent for Magnetic Resonance Imaging

Background:  Gastrointestinal (GI) radiography using barium contrast media has been widely used as a first-choice diagnostic imaging modality for detection of GI pathologies. Colonoscopy is the standard of care for colorectal cancer (CRC) screening.  However, colonoscopy is an invasive procedure that requires intravenous sedation and suffers from patient noncompliance.  CT colonography (CT-C) has high sensitivity to identify large polyps, but sensitivity decreases with polyp size and radiation dosage is a concern.  MRI colonography (MR-C) uses non-ionizing radiation and provides CRC lesion detection with high specificity, yet modest sensitivity.  MR-C has been indicated in cases of incomplete colonoscopy, due to obstruction, and is increasingly being applied as a non-invasive screening tool without the need for sedation. Invention:  A scaffold bearing eight terminal alkyne groups was synthesized from sucrose, and copies of an azide-terminated Gd-DOTA complex were attached via copper(I)-catalyzed azide-alkyne cycloaddition.  This contrast agent (CA) was administered by gavage to C3H mice.  Passage of the CA through the gastrointestinal (GI) tract was followed by T1-weighted magnetic resonance imaging (MRI) over a period of 48 hours.  Thus, a new, orally administered, GI-specific CA for MRI has been developed and successfully demonstrated Advantages:  Targeted contrast agents (CA) for molecular imaging of GI lesions or pathologies may circumvent these many limitations of current MR-C.  CAs that have multiple Gd-chelates per molecule may exhibit increased molar relaxivities (r1), making the CA detectable at lower concentrations than previously developed MR-C agents.  The advantages of such an agent leverage the benefits of strongly enhanced tumors in T1-weighted images, resulting in a significantly lower limit of detectability without the need to use bright or dark lumen methods.  If such an agent were targeted to a cell-surface marker that is specifically expressed in GI lesions or pathologies, but not in surrounding GI tissue, it would provide the benefits of lesion specificity and enhanced sensitivity after unbound agent has cleared from the GI tract. To date a multivalent GI -specific orally available gadolinium MRI contrast agent has not been demonstrated, prior to this invention. Applications:  This is a GI-specific MRI contrast agent.  Key Words:  MRI, contrast agent, gastrointestinal tract. Lead Investigator:  Eugene A. Mash Jr. Licensing Manager:Laura SilvaLauraS@tla.arizona.edu(520) 626-1557

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