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Out of the Darkroomby Dawn Chalaire Imagine, if you can, the practice of medicine without imaging studies: no screening tests to alert patients and physicians to the possibility of a serious illness; no computed tomography (CT) scans to help clinicians make an accurate diagnosis; and no follow-up images to ascertain whether a particular treatment is working. With surprising speed, technologies such as CT and magnetic resonance imaging (MRI) have become indispensable, and imaging techniques are continually improving and finding more and more applications in clinical and research situations. “Over the past five to 10 years, as imaging has gotten better, it has become an integral part of everything we do in clinical cancer care,” said Donald A. Podoloff, M.D., professor of nuclear medicine and diagnostic radiology and head of the Division of Diagnostic Imaging at The University of Texas M. D. Anderson Cancer Center. One indication of the importance of imaging in cancer care is the size of the Division of Diagnostic Imaging at M. D. Anderson. Eight hundred people (107 faculty) in four departments—Radiology, Nuclear Medicine, Diagnostic Imaging Physics, and Experimental Diagnostic Imaging—carry out the division’s missions of clinical care, education, research, and prevention. Each day, faculty and staff in the Division of Diagnostic Imaging perform over 480 CT scans and over 100 MRIs.
Measuring Outcomes Molecularly While the use of CT and MRI continues to increase, the recent emphasis on the development of cancer therapies that target specific molecules or pathways has led to a need for new methods of measuring treatment outcomes. Whereas CT and MRI reveal anatomic characteristics and physical events, molecular imaging focuses on biological processes such as glucose uptake, metastatic receptor activity, and the expression of genes, proteins, and kinases. This molecular information could be used to evaluate response to treatments such as antiangiogenic agents and apoptotic drugs that do not necessarily result in tumor shrinkage and to verify early on in treatment that molecular therapies are reaching their intended targets. “I think the power of it clinically will be that, if the hypothesis is correct, after one dose of the drug, you’ll be able to tell if the patient will respond before the tumor starts to shrink,” Dr. Podoloff said. Such information has “huge economic implications,” Dr. Podoloff added, because clinicians will know within days whether an expensive treatment is working, instead of having to wait weeks for the visible results. Positron emission tomography (PET) is an established method of imaging the regional metabolism of glucose throughout an organ. Because tumor cells are more metabolically active than normal cells, increased glucose uptake can be used to distinguish tumors from normal or necrotic tissue. One of the most promising new technologies to come along in recent years is the combined PET/CT machine. The Division of Diagnostic Imaging currently has two such machines and is in the process of adding two more. These combine the anatomic clarity of CT images with the biologic and metabolic information provided by PET scanning. According to Dr. Podoloff, PET/CT imaging has had an enormous impact on the way patients with lymphoma and lung, esophageal, and head and neck cancers are monitored. It is also being studied in breast and colorectal cancers and in melanoma. “PET/CT scanning is a remarkable joining of information that gives you something that is better than either one of them alone,” Dr. Podoloff said. Although anecdotal evidence suggests that PET/CT imaging will change the way certain cancers are managed, studies analyzing the effect of PET/CT imaging on patient outcomes are still ongoing. Because they combine the technology of PET and CT, PET/CT machines are very expensive. Wai-Hoi (Gary) Wong, Ph.D., a professor in the Department of Experimental Diagnostic Imaging, is developing a PET instrument that could provide resolution similar to that seen with PET/CT, at a fraction of the cost. Another important advance has been the development of technetium-99m-labeled imaging. David Yang, Ph.D., an associate professor in the Department of Experimental Diagnostic Imaging, has discovered a dimer, ethylene dicysteine, that can be used to link the radioactive compound to a variety of drugs, biologic agents, and other compounds of interest, which can then be seen on x-rays. Although technetium-99m imaging has a lower resolution than PET imaging, it is much less expensive and offers an advantage when studying certain structures in the chest cavity and skull because it does not highlight the heart or brain. “The appeal of technetium is that it is readily available and relatively cheap. You can use standard imaging; you don’t need a PET scanner for it,” said Dr. Podoloff. A new metabolic imaging method that measures cellular proliferation and turnover, fluorinated thymidine (FNLT), is currently being evaluated in cancer in a large, multi-institutional Phase III trial. Investigators in the Department of Experimental Diagnostics are using computorial chemistry to develop biologically active compounds, which will be tested in animals before going on to Phase I studies in humans. To test the activity of these compounds, the researchers are using metabolic imaging methods that reveal receptors on cells, gene expression, and other intracellular targets. For instance, investigators are developing a PET imaging technique using epidermal growth factor receptor (EGFR) kinase-specific radioactive tracers to measure the activity of novel EGFR-targeted agents. “This will allow us to do regular, noninvasive monitoring of a drug’s activity in a tumor, and may eventually provide a noninvasive selection criteria for study participants as well,” said Juri Gelovani, M.D., chairman of the Department of Experimental Imaging. “The ability to repeatedly monitor EGFR activity at the kinase level should provide a direct measure of drug efficacy in tumor cells as well as measure phospho-EGFR levels in surrogate tissues such as hair and skin.” M. D. Anderson researchers are also developing imaging techniques for a number of other tissue biomarkers of therapeutic efficacy, such as p53, AKT, Bc12, and others, as well as for monitoring tumor proliferative activity, apoptosis, gene therapy, stem cell therapies, and adoptive cell immunotherapies. “Several of these projects are nearly ready for clinical trials,” said Dr. Gelovani. “Pathologists, with their microarrays, are already doing molecular imaging in vitro,” said Dr. Podoloff. “We want to do the same kind of imaging in vivo. That is what the molecular imaging program is all about.” Going digital “In the not-too-distant future,” Dr. Podoloff said recently, “I can envision a time when patients will come in with a small medical chip that has their history, physical, lab data, and x-rays.” Already, once ubiquitous radiology films are being replaced with digital images saved on computer disks, and clinicians at M. D. Anderson can access imaging studies from anywhere through the institution’s electronic medical records system. This trend toward “radiology without walls,” as Dr. Podoloff calls it, has some interesting implications. First of all, there is currently no global or national standard program or digital format for imaging studies saved electronically. Patients arrive with information on a disk that may or may not be compatible with the institution’s computers. To address this problem, researchers in the Division of Diagnostic Imaging have developed a universal reader that accepts information in any digital format and converts it into one that can be read by the institution’s radiology software. Dr. Podoloff is also leading an effort to determine whether doing away with radiology films altogether might have an effect on other areas of the institution, particularly in the operating room and in conducting clinical trials. New role for radiologists Because of advances in molecular imaging and digital technology, radiologists have moved out of the darkroom and into the midst of the multidisciplinary patient care teams. The practice of radiology is moving away from a modality-oriented approach, in which radiologists are experts in CT or MRI or ultrasound, and toward a disease-oriented approach in which radiologists use all available imaging methods in the imaging of diseases within certain defined anatomic areas.“My vision for radiology is that it will become more and more disease-oriented and much more molecular,” Dr. Podoloff said. For more information on this topic or for questions about M. D. Anderson’s treatments, programs, or services, call askMDAnderson at (877) MDA-6789. Other articles in OncoLog, January 2005 issue:
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