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For other articles and previous issues click here. November 22, 2004 SPECT/CT
— The Future Is Clear Coupling SPECT with today’s high-powered CT scanners has propelled the technology into a number of new research and clinical arenas—from in vivo small animal studies to CT angiography in the emergency department. New tracers already under testing specifically target cancers of the brain, thyroid, prostate, breast, lung, ovaries, kidneys, and liver, as well as heart and bone diseases and defects. With the advent of fusion imaging, nuclear medicine’s potential to diagnose and treat disease has advanced so much that in many ways clinical practice is still catching up. That’s especially true for single photon emission computed tomography (SPECT), where utilizing the power of rapid multislice scanners does more than just speed things up. Like PET/CT, SPECT/CT acquires both scans with the patient in the same position. Specialized registration software then reconstructs the data sets, adjusts for differences in format and scanner geometry, and fuses them into a single image. Grafting the high spatial resolution capabilities of today’s high-speed CT scanners with SPECT’s highly accurate definition of disease processes vastly enhances anatomical mapping and localization, moving the new hybrid directly into a wider range of clinical applications. Most significantly, CT attenuation correction greatly reduces the problems of distortion and degradation that typically occur with radionuclide-based methods. Moving Into Molecular Imaging Molecular imaging with SPECT/CT, however, “is a complete reversal of traditional SPECT imaging” because newly developed SPECT tracers are target-specific, attracted only to the tissues they’ve been designed to find. That means physicians can very swiftly and precisely find—or rule out—particular disease processes. But, notes Rollo, “We don’t have attenuation algorithms or correction methods that apply to anything other than technetium to improve localization of the area of activity.” That’s where CT comes in. It doesn’t rely on the energy output of any particular tracer to produce images. It offers a reliable, precise mechanism for creating attenuation correction maps for any radioisotope, thereby boosting the accuracy of lesion definition in nuclear medicine. Moreover, because SPECT radioisotopes typically have long half-lives, they enable monitoring tissue changes over time, further strengthening the ability to narrow down the characteristics of a specific disease process. And the high specificity of SPECT tracers means that more than one agent, each emitting a particular energy level, can be injected to track related processes simultaneously. To take advantage of both these attributes, an array of new SPECT tracers are currently being developed to carry radionuclide therapeutic agents to the disease site. The goal is to be able to pinpoint both the disease process and its ongoing response to targeted treatments. “It’s important to understand that it’s one exam; you put the patient on the table once, and the scanner gathers the CT data set and the nuclear medicine data set in one procedure so that these can be precisely overlaid. The power of hybrid imaging comes from adding the two sets together, [giving you] the ability to see anatomical information simultaneously with metabolic information,” says Markus Lusser, vice president, global sales and marketing, of Siemens Medical Solutions’ nuclear medicine division. The Siemens’ Symbia TruePoint SPECT/CT integrated scanner can perform conventional SPECT, multislice CT, or SPECT/CT studies using a single system. The product line also makes full use of the company’s syngo multimodality applications software. Adding CT attenuation correction is proving “absolutely essential” for anatomical landmarking and improving specificity, says Lusser. “[Many customers] have had cases where you don’t see anything on the nuclear medicine image, you don’t see anything on the CT image, but as soon as you fuse them and deploy attenuation correction … and visualization techniques, all of a sudden you get a diagnosis.” Developers and users agree that improved attenuation correction is one of SPECT/CT’s strongest points. “Other methods are like consumables—it wears out over time and the quality degrades,” points out Michelle Heying, general manager for nuclear medicine at GE Healthcare. “Integrated CT scanning gives you the ability to complete the scan—say a cardiac exam—without degradation.” GE pioneered the first commercial SPECT/CT in 1999, integrating its Infinia SPECT with the Hawkeye CT. GE’s is the only system combining both cardiac SPECT and PET with a nondiagnostic CT scanner. Clinical Advances “If you look at nuclear medicine in general, it’s about 50% oncology and 50% cardiology,” points out Leo Gurvich, Philips’ SPECT/CT product manager. “The most important requirement is to have a high-end CT, 16-plus-slice or higher.” He adds that for other proven applications, like localizing and treating infection, lower-resolution SPECT/CT scanners still perform better than SPECT alone while providing many users with a lower-cost first step toward the more powerful systems. Rollo emphasizes, “It’s not just research. SPECT/CT [will make] the difference in the diagnosis in terms of earlier definition of the disease and therefore more appropriate treatment and management of that patient.” A number of studies, including ones from the Mayo Clinic and Vanderbilt University, show that as many as one-quarter of cases result in “either a change in patient management or in patient diagnosis as a result of the SPECT/CT exam,” says Frank Anstett of GE Healthcare Global Clinical Validation. “If we do a weighted average, we can expect to see those changes following SPECT/CT about 25% of the time.” He adds that some studies for specific diseases report still higher findings, notably Johns Hopkins cancer research showing a 58% improvement in information. Table 1 on page 34 provides a sampling of current and anticipated SPECT/CT applications and molecular imaging radiopharmaceuticals already under study. And Table 2 on page 36 lists various clinical studies by title and type and shows the change in care management or interpretation resulting after SPECT/CT exam. Siemens’ Lusser realizes that many users and industry observers will use PET/CT as their initial reference for the newer hybrid. “From a historical perspective, the merging from pure PET to PET/CT has been a tremendous success and it points the way [for SPECT/CT to grow],” he says. “But there’s not necessarily an overlap between the two modalities; it’s more that they are complementing each other.” “It’s an important point, the difference between where PET and SPECT are now,” concurs Gurvich. While PET is extremely sensitive, capable of providing exquisite imaging quality under proper conditions, he adds, “it’s often cost-prohibitive for cardiology.” For example, the cost of a generator for making the PET agent rhubidium 82, for imaging infarcts, costs on the order of $30,000 per month. That compares to the average $25 to $30 cost per dose of technetium or annexion SPECT/CT uses to show ischemia or infarct, respectively. More importantly, says Rollo, “part of the molecular imaging concept is not just to provide a diagnosis but also to be able to use the same molecular probe for therapy. Once we have agents that identify the presence of disease [and] the CT to make sure we localize the areas of abnormality, then we can take that same agent and label it with therapy. So we avoid the typical complications that accompany conventional chemotherapy and even radiotherapy … and end up with a highly-specific therapy to treat the cancer only.” The difference is clear, says Rollo. “There’s no fluorine [PET’s key agent] that can be replaced with therapy. There are potentials … but right now, you can already do this with SPECT.” Forward Thinking Lusser agrees. “In the short term, we can expect many new users—maybe even more than the industry predicts—to purchase SPECT/CT [over conventional SPECT]. We know that one integrated device creates better clinical results than two separated devices, so it’s going to be the platform of choice.” The trend toward hybridization is crucial on several counts. With SPECT historically paying less than PET (and PET reimbursement itself troubled by recent Centers for Medicare & Medicaid Services cuts), hybrids today provide users with more clinical options at more affordable prices. The current generation of scalable systems allow purchasers to select and expand both hardware and software components as needs and finances change. In the not-too-distant future, all the experts anticipate
that fusion imaging’s capabilities will fuel development of
still more sophisticated tracers, designed not only to image diseased
tissue but also to help minutely track treatments. “We expect
to see SPECT/CT move well beyond a diagnostic imaging product to
reimaging for response to therapy. Adds Heying, “We’re going to look back in five, seven, or 10 years and not recognize the systems. Where we’re going is all about breakthrough.” These predictions have different implications for different users, Lusser says. “If you’re buying a CT scanner, you need to think about all the applications you can use it for at the end of the day. Our customers keep asking, ‘In the future, will every CT have some kind of metabolic imaging device attached to it?’ If you think of nuclear medicine as a very specific, metabolic, smart contrast media … that might very well be the case, five years or so down the road.” — J. K. Bucsko is a freelance healthcare writer and editor based in Westville, N.J.
“We think that cardiac studies will become one of the major clinical opportunities,” says Philips’ David Rollo, MD, PhD, FACC. For example, using BMIPP [15-p-[123I]iodophenyl-3-(R,S)-methyl pentadecanoic acid], a new agent that labels free fatty acids with iodine-123, patients who arrive at the emergency department having experienced chest pain within the past half hour can be ruled in or out almost immediately as heart attack victims. As Rollo explains, “The normal portion of the heart would fill in with free fatty acids, but the area of ischemia would be absent of activity [on the SPECT/CT scan]. Given [BMIPP] within 10 minutes of arriving, the patient could be referred to the cardiac catheter lab or to therapy. Compare that to what happens today, where it takes at least 12 hours for test results to return.” Cardiac SPECT/CT may have especially significant implications for women whose chest pains are more often dismissed or misdiagnosed. He notes: “What’s really important about the BMIPP is that it not only turns positive within 20 to 30 minutes of the cardiac event, but it stays positive for almost two weeks.” Similar benefits accrue for the otherwise-seemingly healthy patient (like former president Bill Clinton) whose conventional serial enzyme studies returned as normal. “The new [targeted] imaging marker allows us to determine [the specific cause of chest pain] and … salvage cells that would otherwise die.” Because SPECT/CT allows detecting and localizing old calcium and new plaque for definitive study, Rollo also anticipates that it will soon become the standard follow-up study after procedures such as a percutaneous transluminal coronary angioplasty or stent; he notes that research is being planned at DeBakey Heart Center, Houston’s Methodist Hospital, Johns Hopkins, MD Anderson Cancer Center, and Cedar Sinai, among others. In cancer, one of the biggest SPECT/CT success stories to date has been in the treatment of non-Hodgkin’s lymphoma patients. Some 60% of such patients are typically refractory. But, according to Rollo, using Zevalin labeled with indium-111 for imaging plus yttrium-90 for therapy, 80% of those treated with Zevalin respond, with nearly 50% going into total remission. “So of the 60% who would otherwise die, half end up with their disease going away,” he notes. “And 80% have some positive response from molecular imaging therapy. That’s pretty impressive for an outpatient treatment.” — Source: GE Healthcare Global Clinical Validation 2004. All studies performed with the GE Infinia Hawkeye.
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