MRI Contrast Agent Prototype Targets Cancers

December 14, 2011

University of Pennsylvania researchers have developed an experimental MRI contrast agent capable of targeting tumors, according to a report in the journal ACS Nano. Its coating, instead of targeting particular cancer receptors - which can be hit-or-miss and depend on the cancer - is attracted to the acidic environments in which tumors generally thrive.

University of Pennsylvania researchers have developed an experimental MRI contrast agent capable of targeting tumors, according to a report in the journal ACS Nano. Its coating, instead of targeting particular cancer receptors - which can be hit-or-miss and depend on the cancer - is attracted to the acidic environments in which tumors generally thrive.

The research was done by associate professor Andrew Tsourkas, PhD, and graduate student Samuel H. Crayton of the department of bioengineering in Penn’s School of Engineering and Applied Science.

“One of the limitations of a receptor-based approach is that you just don’t hit everything,” Tsourkas said. “It’s hard to recommend them as a screening tool when you know that the target receptors are only expressed in 30 percent of tumors.”

In contrast, the approach his team developed exploits the fact that almost all tumors exhibit a change in the acidity of their environment.

The Penn engineers took advantage of something known as the Warburg effect, a quirk of tumor metabolism, to get around the targeting problem. Unlike healthy cells, cancerous cells use an anaerobic process for their energy, turning glucose into lactic acid. But unlike normal muscles, tumors disrupt the blood flow around them and have a hard time clearing the acid away, lowering pH in surrounding tissue.

By using glycol chitosan - a sugar-based polymer that reacts to acids - the engineers allowed the nanocarriers to remain neutral when near healthy tissue but to become ionized in low pH. The altered charge that occurs in the vicinity of acidic tumors attracts and retains nanocarriers.

The researchers hope that within seven to 10 years glycol-chitosan-coated iron oxide nanoparticles could improve the specificity of diagnostic screening. The ability to accurately detect sites of malignancy by MRI would be an immediate improvement to existing contrast agents for certain breast cancer scans, they added.