Imaging Program looks toward the future

Mark “Marty” Pagel, PhD, who directs CAMEL
Mark “Marty” Pagel, PhD, who directs CAMEL

Arizona Cancer Center scientists are conducting research that they expect will lead to earlier and faster monitoring of a patient’s response to cancer treatments.

Researchers at the University of Arizona’s Contrast Agent Molecular Engineering Lab (CAMEL) say their work could hone diagnostic imaging procedures that would show oncologists how their prescribed treatment is attacking a tumor and provide the physicians with information to quickly change chemotherapy protocols. The expectation is that response to treatment could be determined in 24 to 72 hours versus the current standard of as much as two to three weeks from the time a treatment is administered to a patient.

“These rapid evaluations may relieve the anxiety in waiting for critical test results, and may accelerate a physician’s ability to change the therapeutic regimen in order to tailor the therapy to the patient’s condition,” said Arthur Gmitro, PhD, co-director of the Cancer Imaging Program, one of the Arizona Cancer Center’s five primary scientific research programs. He is also a professor of radiology in the Department of Radiology and professor of optical sciences in the College of Optical Sciences at the University of Arizona.

This individualized diagnostic therapy is called “theranostics,” a term used to describe the proposed process of diagnostic therapy for individual patients - to test them for reaction to a new medication and to tailor a treatment for them based on those test results.

Scientists use magnetic resonance imaging (MRI) to examine molecules in a tumor to see what changes occur as cancer treatment commences. The Arizona Cancer Center team is developing chemical agents to improve the contrast between healthy and diseased tissue.

“We are looking at how quickly a tumor’s blood vessels are being shut down,” said Mark “Marty” Pagel, PhD, who directs CAMEL. Cutting off a tumor’s blood supply curtails its growth.

The contrast agents being developed at CAMEL improve those molecular observations. The initial research is being directed at aggressive metastatic breast cancers that are treated with novel anti-cancer drugs under development by industry partners.

CAMEL has also developed MRI methods that measure the acidity of the tumor tissue. Due to their altered metabolism, tumors tend to be more acidic than normal tissues, which enhances their ability to migrate into surrounding areas and spread to distant tissues. These acidic tumors are often more resistant to standard chemotherapies. Thus, measuring the acidity of a tumor can provide useful information for determining whether aggressive treatment is needed, and which type of treatment will work best.

Enzymes are the “workhorses” of tumor biology, but detecting whether enzymes are actively working in tumors can be a challenge, Dr. Pagel said. CAMEL has patented a novel method for detecting enzymes with MRI and is developing this method to detect enzymes that degrade normal tissues around rapidly growing tumors. This method is also used to evaluate the effects of chemotherapies.

“Just as students at the University of Arizona are graded on their performance on tests and are not simply graded on attendance, CAMEL’s imaging tests that measure the performance of working enzymes in tumors are expected to be a more accurate assessment than the current biochemical tests that simply measure the amount of enzymes,” Dr. Pagel explained.

Because many chemotherapies can cause adverse reactions in patients, there is interest in using nanotechnology to create “nanocarriers” that deliver therapies only to tumors. CAMEL has developed MRI methods to simultaneously track many nanocarriers through the body, which may be used to identify the nanopaticle that shows the best drug delivery within each patient. 

This new diagnostic process, which would work best for solid tumors, would involve a patient undergoing an imaging test to take a “snapshot” of the molecular composition of the tumor just before receiving a chemotherapy drug. The results would provide the physician with the knowledge to select the best therapy for that tumor. 

Immediately after a patient received chemotherapy drugs, he or she would receive a second imaging test to ensure that the drugs were successfully delivered to the tumor. After an overnight stay or a return visit the next day, a third test would show how the molecules in the tumor were being affected by the chemotherapy.

The patient and physician would then have great confidence that the tumor was successfully treated even before the tumor began to change in size. If the delivery or effect of the therapy was shown to be unsuccessful, the patient and physician could immediately plan for a different therapy, saving valuable treatment time.

CAMEL occupies a large chemistry laboratory in the Arizona Cancer Center, which is surrounded by laboratories and research programs led by cancer biologists and clinicians. This interdisciplinary research environment has been critical in focusing CAMEL’s expertise in biomedical engineering and chemistry on the development of new tools for cancer studies.
 
In addition, CAMEL collaborates with the Research Radiology Institute and the strong optical sciences community at the University of Arizona in order to integrate these world-class scientific programs with cancer research in the Arizona Cancer Center. This outstanding interdisciplinary and collaborative research environment was instrumental in attracting CAMEL to move from Case Western Reserve University in Cleveland to Tucson in 2008, Dr. Pagel said.

“The CAMEL has found an ideal home in the desert,” he said.