Time is critical when it comes to diagnosing and treating cancer.

“We want to know if the drugs are killing the tumors within one day because assessing early response is key to cancer treatment and greatly reduces the stress of uncertainty for patients.” Marty Pagel, associate professor of biomedical engineering.

Aggressive cancer tumor cells often produce enzymes that cut into healthy tissues surrounding the tumor, providing routes for tumor cells to escape and create new, difficult-to-treat metastatic tumors. These enzymes could be ideal targets for diagnosing and treating aggressive tumors early on, but they are seldom investigated because accurately measuring their performance has been difficult -- until now.

Marty Pagel, associate professor of biomedical engineering, and a team of UA researchers have developed MRI techniques to quickly, effectively and noninvasively measure enzyme performance in tumors.

As reported in the journal Magnetic Resonance in Medicine, their new technique detected a highly performing enzyme within a mouse model of pancreatic tumor tissue, relative to a lack of enzyme performance in tissue from other areas of the body. “Because we are engineering our MRI tests to meet specific levels of accuracy and precision, having a reliable model of pancreatic cancer has been critical for evaluating our progress,” Pagel said.

The National Institutes of Health is investing about $3.4 million to further develop this biomedical imaging technology at the UA.

The UA team, including chemistry and biochemistry students and faculty, has created chemical sensors that produce imaging signals strong enough to detect subtle changes in the performance of several enzymes and specific enough to detect each enzyme. Faster imaging speeds have made the enzyme measurements much more practical.

“The standard MRI methods took 30 to 60 minutes to obtain results,” said Julio Cárdenas-Rodríguez, research assistant professor of biomedical engineering. “We redesigned these methods to obtain results in less than two minutes.”

Cárdenas-Rodríguez is now leading a team of researchers from the colleges of Engineering, Science and Medicine to translate the fast MRI method to a scanner for clinical trials measuring enzyme activities in the tumors of cancer patients. Collaborators for the clinical trials include Siemens Healthcare, the manufacturer of the MRI scanner; Phillip Kuo, associate professor of medical imaging; and Drs. Alison Stopeck and Pavani Chalasani of the University of Arizona Cancer Center.

Detecting Acids in Tumors

The sooner doctors know how cancer tumors respond to treatment, the more effectively they can treat patients. Being able to measure lactic acid levels in tumors, which are slightly higher than levels in normal tissue, is one way to know early on how well drugs are working.

Just as our muscles produce extra lactic acid during exercise, fast-growing cancerous tumors produce extra lactic acid. Pagel’s research team has spent several years developing a highly accurate MRI method to measure the acid content in tumors.

Students from the UA Cancer Biology Graduate Interdisciplinary Program and the College of Pharmacy are now using the MRI method to evaluate new anticancer drug therapies. In tests with lymphoma tumors, the MRI method detected lower production of lactic acid within 24 hours after the tumors were treated with a chemotherapy drug, indicating that it had reduced or stopped tumor growth.

“We want to know if the drugs are killing the tumors within one day, because assessing early response is key to cancer treatment and greatly reduces the stress of uncertainty for patients,” Pagel said.

Monitoring Effectiveness of Drugs to Treat Pancreatic Cancer

One track of Pagel’s research aims to improve monitoring the effectiveness of drugs that are used to treat pancreatic cancer.

Pancreatic cancer is particularly difficult to treat in part because tumors respond very slowly to drug therapy. In fact, it can take months for the size of a pancreatic tumor to change, making it difficult to assess the effectiveness of drugs.

To speed up the process, Pagel and Joseph Kobes, a UA biomedical engineering graduate student, are developing MRI methods to measure earlier response to anticancer drugs. One of their most promising techniques evaluates how water diffuses through tumor tissue, which is typically limited by the abundance of cells within the tumor. If a drug therapy reduces the number of cells in a tumor, water can more easily diffuse in the tumor. The researchers have shown that the imaging method can detect cellular change in a tumor as early as two weeks after starting drug treatment.

This team is collaborating with the UA Cancer Center’s Emmanuelle Meuillet, associate professor of nutritional sciences and molecular and cellular biology. Meuillet has developed a series of drugs designed to cure pancreatic cancer, and the imaging method lets her more quickly assess their effectiveness.