Molecular Imaging: Seeing Cancer in Action Inside the Body

         

Oct. 8, 2009 – Molecular imaging can reveal how cancer cells communicate, how they move, what they need to survive and where they are vulnerable to attack. In this edition of Breakthroughs in Cancer Research, David Piwnica-Worms, MD, PhD, professor of developmental biology and radiology at Washington University School of Medicine, explains how molecular imaging is different from more traditional radiology techniques and discusses new discoveries coming out of the medical school’s Molecular Imaging Center.

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TRANSCRIPT OF AUDIO FILE

On this edition of Breakthroughs in Cancer Research, we’ll talk about how scientists are making it possible to see cancer in action inside the body. That’s providing new information on how to destroy cancer cells.

Host: Thanks for downloading this podcast from the Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine in St Louis. I’m Gwen Ericson. With techniques collectively called molecular imaging, scientists are finding new ways to detect cancer early, monitor cancer treatment and develop better cancer drugs. Molecular imaging can reveal cancer’s secrets, showing how cancer cells communicate, how they move, what they need to survive and where they are vulnerable to attack. To tell us more is David Piwnica-Worms. He is director of the Molecular Imaging Center at the Mallinckrodt Institute of Radiology and the Siteman Cancer Center. Dr. Piwnica-Worms, thank you for joining us.

Piwnica-Worms: Well thank you, Gwen. I’m happy to talk with you today.

Host: Most of us have had experience with traditional kinds of medical imaging – things like X-rays, PET scans and ultrasound scans. But we’ve probably never encountered molecular imaging. Tell us about the distinction between traditional medical imaging and molecular imaging.

Piwnica-Worms: In most of the traditional medical imaging that we may have experienced as patients or with family members, the focus of the imaging is on the anatomy and, in the context of cancer, on the mass or the size of the mass. But in molecular imaging, we’re actually interested in the details of the molecules that are inside the cancer. That is the biology or the biochemistry or metabolism of the cancer. We’re actually trying to image changes in those molecules and biochemistry that may even precede changes in the anatomy.

Host: Give me an example of a molecular imaging technique.

Piwnica-Worms: One strategy is in the general area that we call genetically encoded reporters. And that means we may take some genetic material from one organism and transfer it into another that may have favorable imaging properties. One such example that we make common use of is firefly luciferase. That is the same firefly that we see flying around in our backyards on a July day in St Louis. And the gene that actually makes the fireflies glow is called luciferase. We can actually use standard molecular biology and cloning techniques to transfer that luciferase gene from fireflies into a cancer cell, and we can watch the cancer glow and move around the body. Or it may tell us how it glows in response to different genes being expressed, or maybe how a protein, one of the building blocks, is processed. And those signals can tell us something about the metabolism and the gene expression inside those cancer cells using noninvasive imaging cameras.

Host: Tell me more about what techniques like that reveal about cancer.

Piwnica-Worms: One way to think of this is that cancer is like a baseball game where we don’t understand the rules. And you can imagine if you were taking a snapshot of Pujols at bat in the first inning, and then sometime later in the third inning you had a snapshot of Holliday running around a base path. And then at some other time, you had a snapshot of Ankiel making a long throw to third base from the outfield. What are the underlying rules that allow that to happen? If you knew nothing about the game of baseball and you had to try to put these together, dynamic views, continuous videos and movie loops would allow you to begin understanding those rules of why sequential events occur in a more dynamic and easy way than a series of random snapshots. And we hope that analogy sort of lets you know how we can look dynamically, continuously, over time with these noninvasive molecular imaging strategies at the baseball game of cancer that’s going on inside the cells.

Host: In medical terms, what can molecular imaging do for us?

Piwnica-Worms: A lot of the activities do relate to preclinical and basic type of cancer biology work. These help us better understand the cancer pathways, the rules that guide the metabolism of the cancer cell. These represent the new targets of tomorrow, where new drugs and combinations of drugs can actually help patients. And in some special cases, maybe even in a human, we can tag the drug and understand, is it actually hitting the cancer? Is it binding to its molecular target? And we can image that noninvasively and repetitively over time. And in another area that relates more directly to patients, there are some techniques like fluorodeoxyglucose (FDG) PET. And this is a special subset of molecular imaging that is available today that does look at sugar metabolism in cancer. It can help us detect cancer at early stages or help guide therapeutic choices. That’s one area of molecular imaging that’s actually in the clinics today.

Host: What are some of the latest discoveries to come out of the Molecular Imaging Center?

Piwnica-Worms: We have a lot of activities going on both within our core groups and collaborators. Two areas of interest that have recently been published and explored involve one of these special pathways. It’s known scientifically as the beta-catenin pathway. It’s very, very important in colon cancer, and it also affects how cells grow and metastasize. And by using one of these luciferase strategies, we can now follow the time course of the regulation of the beta-catenin protein inside colon cancer cells.

Another area that’s been very interesting for us is we developed a new optical technique to look directly at inflammation in living animals. In inflammation that occurs around cancer, there is an enzyme known as myeloperoxidase. And it ends up that a small molecule that many people are familiar with known as luminal – which is the same small molecule that you see on CSI Miami that’s sprayed on blood – has a very highly sensitive response to the enzyme myeloperoxidase, which is one of the key enzymes in inflammation. We’ve developed some techniques now using that luminal where we can now look at this myeloperoxidase-mediated inflammation in mouse models, and maybe someday we might be able to look at that in humans and help us follow inflammatory processes related to cancer.

Host: Tell me about what the Molecular Imaging Center itself is like.

Piwnica-Worms: Well, the Molecular Imaging Center itself is really two main components – a physical center, if you will, and a virtual center. The physical center is the founding faculty investigators who are physically in our laboratory space, all interacting on a daily basis with our laboratories, ourselves and the imaging cores that are in my lab and the investigators’ labs around. And then in addition, we’re tied together by a National Institutes of Health Molecular Imaging Center grant that helps support the cores and the broad array of investigators. We have projects that are ongoing with collaborators in cancer biology and immunology and pharmacology and biochemistry – all interested in studying biology noninvasively through these molecular imaging strategies so that we can try to pry basic biology done with traditional reductionist approaches together with these new dynamic strategies in living cells and live animals and ultimately patients.

Host: Dr. Piwnica-Worms, thank you for joining us.

Piwnica-Worms: You’re welcome.

Host: If you are interested in learning more about the Molecular Imaging Center, please visit its Web site at mic.wustl.edu.