PET Imaging Technology Under Development for Improved Brain Tumor Detection

Dr. Csaba Juhasz, assistant professor of pediatrics and neurology at Wayne State University's (WSU; Detroit, MI, USA) School of Medicine and Children's Hospital of Michigan, will utilize the imaging technique positron emission tomography (PET) to monitor the movement of the tracer alpha [11C] methyl-L-tryptophan (AMT), or a modified form of tryptophan, to areas of the brain where the enzyme indoleamine 2,3-dioxygenase enzyme (IDO) is expressed. IDO, which is present in many kinds of tumors, can remove tryptophan from the tumor tissue, causing tolerance to immune rejection. AMT-PET can detect tryptophan uptake and conversion to its metabolites by IDO, contributing to escape from tumor rejection.

What IDO detection means for brain cancer patients, according to Dr. Juhasz, is an earlier, more accurate detection of tumors, especially in those who have already undergone therapy or tumor removal. "Lots of times patients come back after surgery, radiation, or chemotherapy, and something shows up on the follow-up MRI [magnetic resonance imaging],” Dr. Juhasz said. "And it's very difficult to tell, in some cases, whether you're seeing a recurrent tumor or just some damage from the radiation, which is called radiation necrosis.”

In addition to differentiating tumors from nontumorous lesions, the tracer may also be able to identify tumor type and severity based on the kinetics of AMT uptake observed on the PET scan and the level of IDO expression in removed tumor tissue. "It may have a very high prognostic value in determining how severe the tumor is or the likelihood of survival,” Dr. Juhasz said. "But we are not that far right now; we're just trying to figure out how IDO is expressed in brain tumors and how we can detect it with PET.”

If this technique establishes itself to be useful with brain tumors, it could be applied to detecting other types of cancers where the IDO enzyme is expressed, which include lung, colon, and ovarian cancers. Dr. Juhasz is currently contracted by U.S. National Cancer Institute (Bethesda, MD, USA) to study the same AMT-PET method combined with a computed tomography (CT) scan in lung tumors in collaboration with the Karmanos Cancer Institute.

"If you can apply this to some very common cancer types, it could have much larger implications,” Dr. Juhasz said. "Potential drugs targeting IDO to break tumor immunoresistance are being tested, and AMT-PET may well become a molecular imaging method for selecting patients for such treatments and monitoring treatment effects.”

The PET Center at the Children's Hospital is the only center in the United States that makes the tryptophan tracer AMT, which has been used previously to measure brain serotonin synthesis in various neurologic disorders such as autism and epilepsy. Dr. Juhasz's study is the first in the world to utilize AMT-PET and track IDO for brain tumor detection.

"Dr. Juhasz's research poses the potential for a dramatic improvement in the early and accurate detection of brain tumors,” said Dr. Hilary Ratner, vice president for research at WSU. "Wayne State is proud to play a part in this innovative method of cancer detection, which could be a remarkable step forward in the treatment of multiple forms of cancer.”

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