PHILADELPHIA - Imagine trying to take a picture of a runner, but only being able to see her feet. If you could see her whole body, you'd get the full picture of how she uses both legs to put one foot in front of the other to reach top speed. That's the idea behind a cancer imaging project in the Perelman School of Medicine at the University of Pennsylvania, and the researchers just received $1.4 million in funding from the National Institutes of Health (NIH) as part of the Cancer Moonshot to help the effort along. Researchers at Penn are building a positron emission tomography (PET) scanner that can image a patient's entire body at once, and can also look at two of cancer's food sources at the same time - glucose and glutamine. This grant will help those researchers interpret the data they get from those scans.
"Currently, we can see glucose and glutamine individually, but not on the same scan, which also means we don't know much about how they interact with each other," said the project's co-principal investigator David A Mankoff, MD, PhD, the Gerd Muehllehner Professor of Radiology at Penn and co-director of the Cancer Imaging Core of Penn's Abramson Cancer Center. "The scanner we're building will give us that information, and this grant will be instrumental in helping us apply what we find."
Glucose is a simple sugar found in the blood, and cancer cells feed off it and use it for energy the same way all other cells do. Some cancer cells are more reliant on glutamine - an amino acid also found in the blood - to be their primary food source. During PET scans, patients are injected with radioactive compounds called tracers that let doctors see certain compounds through the body - in this case glucose or glutamine. If tissues are found to be absorbing high amounts of either one, it can indicate the presence of cancer. Current PET devices can only scan one part of a patient's body at a time. Penn's new device - known as PennPET Explorer - will be able to scan the whole body at once. The increased size and performance of the new scanner will also give doctors the ability to see glucose and glutamine at the same time, which ordinarily would require two scans on two separate days.
"It also allows us to make an image with a smaller radiotracer injection, which means more information with less radioactivity," Mankoff said.
"We estimate that will give us between 10 times and 40 times the amount of information that we get from current PET scans," added Joel Karp, PhD, a professor of Radiology at Penn and the co-principal investigator on the project. "It will not only help us see the full body process when it comes to glucose and glutamine, it will also show us the big picture in terms of how the two relate to each other and how they interact."
PennPET Explorer is expected to be up and running as soon as 2019, at which point the exponential amount of new information will present a challenge for the doctors who need to interpret it. Researchers say this is why the grant is so critical.
"This is a project with clearly stated goals, and this grant from the NIH allows us to build the infrastructure we need now so that once the instrument is completed, we can hit the ground running and take advantage of this data and new approaches right away," Karp said.
One approach researchers plan to take is to use machine learning to interpret the influx of PET data. They plan to initially use this big data tool in breast cancer, and Despina Kontos, PhD, an associate professor of Radiology, will lead that effort.
On the clinical side, there are trials already ongoing looking at glutamine inhibitors designed to take advantage of those tumors that are "addicted" to that particular energy source. Mankoff says one challenge is to determine which tumors are glutamine-addicted. In addition, the rest of the body also uses the critical amino acids, so any drug that tries to block it can have unintended consequences. The new approach will allow investigators to look at metabolism in both the tumor and normal organs.
"This new approach can be critical to understanding that process, since it can show us what those off-target effects are," Mankoff said.
Penn is one of two sites in the country building Explorer scanners as part of a consortium funded to build such devices to demonstrate how whole-body PET imaging will enable new ways to study disease. The other is The University of California, Davis, and the two teams have worked closely to help each other. Mankoff also noted the importance of collaboration among multiple disciplines within the Penn community.
"First, we needed a team to build the machine, and once that's done, we'll have to rely on experts in the field of cancer metabolism - an area in which Penn has done pioneering research - to help implement this new method," Mankoff said. "In between the construction of the scanner and the final version of the new method, we have biologists, radiologists, and mathematicians working together. We're enabling precision oncology in a way that could only happen at a place like Penn."
The full NIH grant number is 1R33CA225310-01.
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