Can a PET Improve Leukemia Care?
November 19, 2008

MADISON - Is the chemotherapy working? Is the radiation therapy shrinking the tumor?
The sooner doctors know the answers to those questions, the better they can tailor cancer treatment. Now a University of Wisconsin research team is finding that non-invasive PET scans may provide the answers early during treatment – in contrast to the current long wait needed to determine clinical outcome.

With five clinical trials in progress, researchers in the UW School of Medicine and Public Health (SMPH) recently reported a promising advance at the 2008 annual meeting of the American Association of Physicists in Medicine. It was a small study involving adult patients with acute leukemia.

The team, led by Robert Jeraj, SMPH assistant professor of medical physics, in collaboration with Mark Juckett, associate professor of hematology, found that a PET scan performed during the first few days of treatment using a substance taken up by leukemia cells predicted which patients were going to respond to chemotherapy and which were not. Both Jeraj and Juckett are members of UW Paul P. Carbone Comprehensive Cancer Center.

“By knowing whether chemotherapy will work or not for a patient right after treatment is started, physicians could stop the ineffective treatment and possibly change to a more effective regimen,” says Jeraj, who also has appointments in the human oncology and biomedical engineering departments.   

Almost one-third of leukemia patients do not respond to chemotherapy, which kills the cancerous cells that originate in bone marrow as well as healthy bone marrow cells. The treatment often severely compromises patients’ immune systems, leaving them highly vulnerable to infections.

Unfortunately, doctors can’t tell how the treatment is going until they perform a bone marrow biopsy--typically on the pelvic bone--after a week-long course of chemotherapy. Two weeks later, a second biopsy is usually taken to confirm that the disease is in remission.

The SMPH researchers took PET scans after injecting study participants with tiny amounts of the radioactive tracer FLT--fluoro-L-thymidine--which is readily taken up by cells during growth. In the scans, FLT shows up as a bright contrasting color in all bones in which bone marrow cells--the most proliferative in the body--are functioning. The researchers compared the scans to biopsy results.

“The scans were completely dark in patients who were responding,” says Jeraj, “while we saw residual bone marrow activity in the scans when the chemo was not successful.”

What’s more, a PET scan shows a total-body picture of bone marrow activity, while a bone marrow biopsy shows activity in only the spot that is tested.

“A measurement at one site doesn’t necessarily represent all activity,” says Jeraj.
The FLT PET scans may also be used to assess how well chemo or radiation therapy is proceeding in the treatment of tumors.

“Tumors exhibit more proliferation than the rest of the cells in the body, so you can see that activity very clearly on a FLT PET scan,” Jeraj says.

FLT is becoming a top candidate for treatment response assessment, and the SMPH, a leader in medical imaging, is poised to contribute to its advancement. The logistically challenging work, under way at only a handful of medical centers, involves multiple teams of experts—physicists, chemists, radiologists, oncologists—and highly sophisticated equipment. Understanding how things look and act before, during and after treatment is the crux of the matter.

SMPH physicists, under the leadership of Jerry Nickles, professor of medical physics, use a 30-ton cyclotron to create the radioactive isotopes and then radiochemists step in to synthesize the compounds and verify their quality. Next the clinicians are involved, enrolling patients, administering the FLT, doing the scanning and finally analyzing the images.

“It takes a lot of effort to align so many people,” says Jeraj.Nevertheless, he and his colleagues are excited by the promise of the new technology. “If PET technology is a better biomarker of treatment response than other measures,” he says, “then clearly it will be used.”