Innovative Imaging May Allow Earlier Cancer Diagnosis

ABSTRACT: Every 3 years, the National Cancer Institute (NCI) asks cancer researchers, advisory groups, and advocacy organizations to recommend important areas to which it should devote additional resources. NCI defines such "extraordinary opportunities for investment" as "broad-based, overarching areas of scientific pursuit that hold tremendous promise for significantly expanding our understanding of cancer." This is the second in a series of interviews exploring the progress and promise of NCI’s six current extraordinary opportunities: genes and the environment, cancer imaging, defining the signature of cancer cells, molecular targets of prevention and treatment, research on tobacco and tobacco-related cancers, and cancer communications.

BETHESDA, Maryland—Improvements in medical imaging over the last quarter century have greatly expanded early cancer detection and the accuracy of diagnosis. Yet imaging’s potential for detecting specific activity within cells, helping develop and target new therapies, and assessing prognosis remains in an early stage.

The National Cancer Institute (NCI) has set the goal for its extraordinary opportunity in cancer imaging as the "accelerated discovery and development of imaging methods that will predict clinical course and response to interventions."

In this interview, Ellen Feigal, MD, acting director of NCI’s Division of Cancer Treatment and Diagnosis, discusses the Institute’s program with Patrick Young, ONI Washington Bureau Chief.

Oncology News International: How does NCI define cancer imaging in the year 2002?

Dr. Feigal: We are not talking just about anatomic imaging, but also about identifying the physiological, cellular, and molecular processes that are taking place in the human body. The ability to image the molecular changes associated with a tumor cell will improve our ability to detect and stage tumors, select appropriate treatments, monitor their effectiveness, and determine prognosis.

To accomplish this will require integrating the growing body of scientific knowledge in tumor genetics, molecular biology, and biochemistry.

ONI: How would you compare cancer imaging today with, say, 25 years ago?

Dr. Feigal: It has come a long way. The resolution of the images has improved greatly, and so has the amount of information that we gain from these images. Technological advances have brought an enormous increase in the spectrum of imaging techniques available to evaluate patients with cancer. These include x-ray, ultrasound, computed tomography, nuclear imaging, and, more recently, fusion technologies combining anatomic and functional imaging.

ONI: What are the most promising new areas of cancer imaging?

Dr. Feigal: There are many areas, but let me highlight a few that can help address major unmet clinical needs. A critical challenge is to integrate knowledge from the incredible advances in genomics and proteomics with imaging to facilitate the development of more effective therapies.

We’re expending a major effort on the development of molecularly targeted therapies, and we think imaging can help find the answers to some critical questions. Does the drug reach its target? Does it modulate its target and affect the downstream pathways? Is there a correlation with the effects on the tumor and the effects on the target and pathway?

We see using imaging across the spectrum of cancer to help us identify precursors to cancer and cancer at an early stage. This may possibly lead to more precisely determined doses and therapies that are less toxic to normal tissues.

Distinguishing indolent from aggressive cancer at diagnosis is a major challenge. A specific example is prostate cancer, in which the ability to distinguish between these types could allow more appropriate treatment strategies.

Questions we think imaging could help answer include: Does the imaging correlate with biomarkers? Does it predict response to treatment? Does it predict clinical outcome?

ONI: What is NCI doing to facilitate these areas?

Dr. Feigal: We have a large number of funding initiatives to stimulate and facilitate imaging research. Let me give you several examples.

NCI-supported In Vivo Cellular and Molecular Imaging Centers carry out multidisciplinary research on cellular and molecular imaging. The objective is to narrow the gap between the discovery of new cancer genes and intracellular pathways and the translation of these discoveries into clinically useful, minimally invasive imaging approaches to expand our understanding of cancer.

The Small Animal Imaging Resource Program develops and applies a wide variety of functional, quantitative imaging modalities. Working with NCI’s Mouse Models of Human Cancer Consortium, researchers will help develop and validate new preclinical models, and design and test imaging techniques to detect human cancer.

The Development of Clinical Imaging Drugs and Enhancers Program fosters and speeds the development of promising imaging enhancers and molecular probes, and their translation from laboratory synthesis to Investigational New Drug Applications.

Finally, the Early Clinical Trials of Novel Imaging Probes is a program that conducts initial human studies for feasibility and proof of concept, and the American College of Radiology Imaging Network is a national network of investigators conducting early- to late-phase clinical trials of imaging technologies.

ONI: Is NCI working with companies to develop imaging techniques?

Dr. Feigal: Yes. NCI is working on a variety of different initiatives and interactions. We have an Interagency Council on Biomedical Imaging and Oncology. Staff from NCI, three centers at the Food and Drug Administration, and the Centers for Medicare and Medicaid Services meet in a confidential setting with product developers in academia and industry. The council provides information and advice to developers about what they need to do to take their products through development and approval (www.nci.nih.gov/scienceresources/announcements/imaging.html). We also have an open, national forum on Biomedical Imaging in Oncology that is held annually (http://cancer.gov/dctd/forum). The council and forum also enable the agencies to learn how the other agencies work, which is important because, as new products come on the market, there may be new challenges that we need to face. We may have to rethink the types of evidence and information that we need as new products get developed. So it helps to go through this process together.

ONI: To what extent have new techniques entered clinical testing or practice?

Dr. Feigal: We are at the early stage in developing the very innovative products, such as molecular probes and contrast agents. But there are very interesting imaging technologies being developed, including using PET to look at the response of tumors to Gleevec (imatinib mesylate).

ONI: How would imaging help you assess the effects of a new drug?

Dr. Feigal: It is possible, say, that it could show the molecular or physiological process that precedes an anatomic change in tumor size.

ONI: How will new imaging technologies improve radiotherapy?

Dr. Feigal: They could help define the tumor bed in a more delineated fashion so that you could direct the most intense amount of the beam to the actual tumor bed. Sometimes it is very difficult to tell a tumor from swelling and other aspects on an image. If you could target the beam in a very defined way, you would cause less damage to normal tissue.

ONI: Would you like to hazard a guess at what the state of cancer imaging will be 10 years from now?

Dr. Feigal: I think we will progress from defining anatomic location to noninvasively identifying the molecular, physiological, and cellular changes.

Perhaps we won’t need to think of imaging as involving big, bulky devices located in discrete centers. There are some very innovative techniques with imaging—for example, swallowing a capsule and having it traverse the GI tract and send spectra or some kind of image.

There are going to be many creative ways to image the body, and you can envision all kinds of exciting ways to capitalize on molecular biology and its translation into imaging technologies. I see the benefits of imaging emerging across the whole spectrum of cancer.