PET brings new definition to brain tumor diagnostics

PET imaging to diagnose brain tumor and monitor recurrence after treatment is an evolving field of research. Investigators at the Radiological Society of North America meeting presented studies revolving around five tracers, as well as various permutations of imaging combinations such as FDG-PET with MR spectroscopy. While results are promising, challenges remain before any of these research avenues becomes clinically routine.

"We don't have definitive answers as to the best way to diagnose and monitor treatment for brain tumors," said Dr. Satoshi Minoshima, vice chair for research in the radiology department at the University of Washington, Seattle.

Researchers' knowledge of molecular imaging is increasing, but more work needs to be done to understand physiology based on basic technology and correlate that knowledge with outcomes, said Minoshima, who chaired a session on brain imaging.

Imaging methods to diagnose brain tumor, guide biopsies, and evaluate residual tumor require different aspects of biomedical information. In the near future, therapy will be based on targeting specific molecular mechanisms of tumors. When that happens, imaging strategy must evolve to provide better surrogate markers, he said.

In one study, Dr. Yuka Yamamoto, a radiologist at Kagawa Medical University in Japan, and colleagues found that the radiotracer carbon-11 methionine was more sensitive than C-11 acetate and FDG in detecting brain tumors. The researchers didn't totally discount C-11 acetate, however, saying it has potential. They observed C-11 methionine uptake in all 14 malignant tumors in the study, C-11 acetate uptake in 12, and FDG uptake in five.

Dr. Badreddine Bencherif, an assistant professor of radiology at the University of Pittsburgh, and colleagues are looking for imaging surrogates that correlate with immunohistological proliferation indices. They found that F-18 fluorothymidine (FLT) could be used as an indicator of brain tumor cell proliferation. Using kinetic modeling, they found a significantly higher net influx and transport of FLT into the tumor as compared with the brain. FLT uptake in the tumors correlated significantly with proliferation. Two patients had low influx and low proliferation, while one had high influx and high proliferation.

"While this is a small study, it gives us an idea of how we might be able to stratify tumors based on their aggressiveness and therefore choose more effective treatment," Bencherif said.

The Pittsburgh group, led by Dr. James Mountz, director of neuro-nuclear medicine, also tested the ability of MRS to help detect recurrent brain tumor after radiation and/or chemotherapy. While the technique showed a high number of false positives, the researchers concluded that it can be complementary to FDG-PET. They evaluated 14 patients with treated brain tumors. In six high-grade tumors, MRS was positive in four with recurrence, but it also was positive for the two without recurrence. PET had three true positives and two true negatives.

In five of the eight low-grade tumors without recurrence, MRS was positive in four, with only one true negative. PET was true negative for all five, with two true positives. Both Pittsburgh studies were reported by Dr. Ashok Muthukrishnan.

Early assessment of therapeutic efficacy helps determine whether treatment should be continued. Dr. Michael Paldino, a radiology resident at Duke University, and colleagues found prognostic significance between FDG uptake and contrast-enhanced MRI findings in patients undergoing intracavitary radiation therapy for high-grade gliomas.

From 10 patients, researchers evaluated 37 coregistered PET and MRI studies. Enhancing lesions with a volume of more than 15 cc and a mean activity ratio greater than 1.2 on PET were associated with decreased survival.

"We are able to define specific characteristics of MR and PET imaging associated with a decrease in survival in a therapeutic setting. These results raise the possibility that a quantitative analysis of CE-MRI and FDG-PET may be able to help identify treatment failure in patients with high-grade gliomas," Paldino said.