MRI Contrast Agent May Detect A Harbinger Of Cancer Drug Resistance

Magnetic resonance imaging is a powerful tool for locating tumors. It may soon also help clinicians choose a course of treatment. Mark D. Pagel and colleagues at the University of Arizona have developed a new contrast agent to detect the activity of an enzyme, transglutaminase, which is associated with tumor growth and drug resistance (J. Am. Chem. Soc. 2013, DOI: 10.1021/ja400254e). Prior attempts to detect transglutaminase in tissue by MRI sometimes yielded false positives on normal tissue surrounding tumors. So Pagel’s team developed an agent with an easy-to-follow change in MRI signal. The group’s contrast agent features an amine side chain that transglutaminase recognizes. The enzyme cross-links the contrast agent to proteins on a tumor, forming an amide bond that generates a signal in an MRI technique called chemical exchange saturation transfer (CEST). Some of the contrast agent may remain in tissues without being cross-linked, but it generates a different CEST signal so it can be disregarded. The agent has not yet been tested in live animals or people. But if it can detect transglutaminase activity in a tumor, it could indicate drug resistance, which would dictate treatment decisions.