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For other articles and previous issues click here. October 25, 2004 Just
What Is Molecular Imaging, Anyway? Everyone in radiology is talking about molecular imaging, but few clinical radiologists seem to be able to define it. It’s not surprising that many clinical radiologists cannot say exactly what molecular imaging is or does, says David Rollo, MD, PhD, FACC, FACN, chief medical officer of Philips Medical Systems of Bothell, Wash. “The fact is the majority of radiologists are still very busy trying to make pictures and providing a diagnosis using traditional imaging, whereas only a few radiologists are aware of the limited number of molecular imaging agents currently available,” he says. “It’s no wonder most radiologists don’t know what the present or future applications are or may be.” Enormous Potential “Most practicing radiologists think molecular imaging has to wait for the development of new contrast agents and equipment and so on, so they can afford to wait to learn about it,” says King C. Li, MD, MBA, associate director of the National Institutes of Health (NIH) Clinical Center in Bethesda, Md. “But that is not what the reality is. The reality is new contrast agents and molecular imaging techniques are being developed and hitting the market every year.” James Thrall, MD, radiologist-in-chief of Massachusetts General Hospital and a professor of radiology at Harvard Medical School, believes the potential for molecular imaging is enormous and that in the age of molecular medicine, which we have already entered, “radiology’s part promises to be significant.” Indeed, the American College of Radiology (ACR) is so convinced of the growing importance and long-term potential of molecular imaging in the clinical practice of radiology that in fall 2001 it established a Commission on Molecular Imaging, of which Thrall is the chairman. The commission has produced a primer on molecular imaging for its members that consists of two parts: a review of clinical molecular imaging methods and a glossary of terms encompassing the concept and lexicon used in the molecular imaging literature. The 32-page primer was distributed as a supplement to its January Journal of the American College of Radiology. The ACR commission is also producing a DVD on molecular imaging, which it plans to distribute to its members—at no charge—later this year, says Li, who is on the ACR committee producing the materials. Radiology Curriculum In 2000, the Society for Molecular Imaging (SMI) was established to advance the understanding of biology and medicine in the context of the living body. Membership in the organization is open to all persons who share the vision of the organization and have educational, research, or practical experience in some aspect of molecular imaging. More than 800 academic and industry researchers attended its third annual meeting in St. Louis in early September. It was the largest meeting dedicated exclusively to molecular imaging. This year, the Society of Nuclear Medicine (SNM) established a Center of Molecular Imaging. The SNM’s tag line is “advancing molecular imaging.” While molecular imaging is the buzz, experts are quick to point out that it is not new. “The principle of using molecules to do imaging has been around for decades, so in some sense, molecular imaging has been with us for quite some time,” says Peter S. Conti, MD, PhD, professor of radiology, clinical pharmacy, and biomedical engineering at the University of Southern California (USC), as well as director of the USC Positron Imaging Science Center and Clinic. Conti is also president-elect of the SNM and chair of Molecular Imaging Corp.’s medical advisory board. Rollo defines molecular imaging as the combination of new molecular agents with traditional imaging tools to capture pictures of specific molecular pathways in the body, particularly those that are key targets in the disease process. The concept has been around for roughly 30 years, but only within the past 10 years has it been put into more widespread practice, he says. It helped greatly, he says, when in the 1990s significant funding from the NIH and other agencies became available to further molecular imaging. “This funding helped spur research into a broad range of clinical applications.” Also, he says, the completion of the first part of the human genome project—which mapped the genes in the human body—in 2000 has led to a greater interest in molecular imaging because scientists can now provide more individualized treatment. Beyond PET Thrall says that had those in nuclear medicine thought of the term “molecular imaging” first, it might have called itself that. “Interestingly,” he says, “the nuclear medicine community, of which I am a member, is very disappointed that it did not.” However, Thrall says, molecular imaging is more than nuclear medicine and not any one particular imaging technique. “It is really a unifying theme around the ability to image at a molecular or cellular level.” While emphasis today is on highly sensitive nuclear medicine techniques, researchers expect that all imaging modalities will soon be affected by molecular imaging, Rollo says. “There is already active molecular imaging work using MRI, ultrasound, CT, and optical imaging.” A number of molecular agents are already in clinical trials. Some scientists believe they will be readily available in as little as three to four years, although most view 2010 as a realistic time frame for molecular imaging techniques to be available and actively “in use.” Rollo says researchers have already made significant progress toward refining a number of important molecular imaging applications for cardiovascular disease and for cancer, particularly of the breast, prostate, lung, bowel, and liver. Future Applications • Finding targeted cells. Cancer cells have an increase in metabolic activity in comparison with normal cells. This fact makes it possible to image cancer cells in vivo using deoxyglucose, a metabolic substance that is voraciously glycolized and trapped by targeted cancer cells. By labeling deoxyglucose with a radioactive agent and injecting the resulting molecular imaging agent into patients, scientists can make nuclear images of the primary tumor as well as metastatic sites throughout the body. This is what FDG PET is all about. • Assessing the effectiveness of therapy. The object of some therapies—such as those used to treat cancer—is to kill specific types of cells in the body. Other therapies such as angiogenesis drugs are designed to promote the growth of new blood vessels and thus healthy cells. Because molecular imaging can target and illuminate both cell death and cell growth, it can tell physicians whether or not specific therapies are having their desired effect. For example, it can tell oncologists whether or not chemotherapy is effectively killing cancer cells or cardiologists whether or not an angiogenesis drug is creating new blood vessel growth in a damaged heart. Physicians can use this information to decide whether to change or keep a patient’s therapy regimen. For example, when chemotherapy or radiotherapy is used to kill cancer cells, apoptosis occurs. Apoptosis is the necessary death of cells to make way for new cells and to remove cells where DNA has been damaged to the point at which cancerous change is likely to occur. If the chosen therapy is effective, apoptosis can be demonstrated within 24 to 48 hours. Physicians can use molecular imaging to determine whether or not apoptosis has occurred and can change the therapy if it does not. Not only does this ability mean that the treatments used will be more effective, but further costs associated with ineffective therapy can be avoided. • Delivering therapy to targeted cells. If therapy is proving effective, annexin could be used as a delivery vehicle to further enhance cell death. Physicians would add a payload of radioactive toxin to annexin. When injected, the “loaded” annexin will deliver the toxic agent to the site of the dying cancer cells to cause even more cells to die. This process creates a cycle of cell death because the more cells that die, the more toxin-loaded annexin will be attracted to the cancer site. This molecular chain of events helps accelerate the therapy’s effectiveness. Local Delivery Molecular imaging provides radiologists with the opportunity to play an increasingly important role in patient care because they are going to be called upon not only to detect the presence of disease but also to apply therapy, Rollo says. Molecular imaging is also a benefit to patients because with a more specific diagnosis, the physician can offer “less troublesome treatment that can be done on an outpatient basis,” Rollo says. “With targeted therapy, you’re treating the disease and not the whole body as you traditionally do with chemotherapy.” Currently, Rollo says, there are nine FDA-approved molecular imaging agents in nuclear medicine with dozens more in clinical trials, including two therapeutic agents, Zevalin and Bexxar, which are approved for treating certain types of non-Hodgkin’s lymphoma and being researched for other possible uses. (Radiology Today recently published an update on Zevalin and Bexxar. See “Expanding Radioimmunotherapy” in the September 25 issue.) Conti says the next challenge for radiologists will be to determine which molecular imaging modality best answers the questions they are being asked. Attempting to use one technique for all investigations won’t work. When it comes to this promising scientific field, radiologists are in an enviable position, Rollo says. “The key to the whole thing is, as the name suggests, imaging,” he says. Because imaging is their specialty, radiologists “have access to diagnostics, therapy, and follow-up management.” Molecular imaging and its many potential applications will provide an opportunity for radiologists to participate more in the diagnoses as well as the follow-up treatment of patients, Rollo says. “They can become very much in the center of therapy.” Start Now Rollo says many disciplines, including cardiology and oncology, are likely to vie for such an important role. That’s why, he says, it is imperative that radiologists not only understand molecular imaging and its many possibilities but also become involved in the development of training programs for molecular imaging therapy. “Failure to do so will have devastating consequences to the future of radiology, which could become only a commodity service primarily in the hospital setting,” he says. — Beth W. Orenstein of Northampton, Pa., is a freelance health writer and frequent contributor to Radiology Today. |
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