The field of medical imaging has been witnessing an extended period of remarkable technological achievement. PET and SPECT?one relatively new player in nuclear medicine and one old standby?are in the thick of these innovative times, and they’re both helping to redefine many aspects of diagnostic imaging.
Both PET and SPECT scans produce tomographic images of a patient by detecting radiation that is emitted following an injection of a radioactive tracer. The tracer helps determine whether disease is present by indicating changes in physiological activity.
“The primary applications for PET are for oncology?soft-tissue tumors?which accounts for roughly 90 percent of all clinical utilization,” says Jonathan Frey, director of product and clinical marketing for Siemens Medical Solutions (Knoxville, Tenn). “The remainder make up mostly cardiac exams and a small number of neurological studies.”
David Rollo, MD, PhD, chief medical officer for Philips Medical Systems (Milpitas, Calif), says, “In order to do a PET study, the indication for pretty much all of the applications is that you have a positive CT or MR study, and you’d like additional information in terms of specificity of the area of abnormality.
“MRI and CT are sensitive in defining that disease is present, but they aren’t specific in determining what particular type of disease may be present,” continues Rollo, adding that prior to PET, surgical procedures or biopsies were the only ways to determine specificity. “PET dramatically changed that. The increased metabolic activity not only [confirms] that cancer [is present] but provides evidence of staging or metastasis beyond the primary.”
Clinical utilization of PET began in the 1990s; SPECT has been around for decades. SPECT scans are used for a host of applications in nuclear medicine, with the majority of studies being cardiac-related. “Around 55 percent of SPECT exams are indicated for coronary artery disease, mostly myocardial-perfusion studies,” Frey says. “Bone scanning accounts for another 25 percent of the applications, and 25 percent are miscellaneous.” Among the last category are scans of the brain, prostate, and thyroid.
While SPECT is preferred over PET for most cardiac cases, 15%?20% of these cases are inconclusive due to complicating factors and require an alternate study, says Karthik Kuppusamy, general manager of PET/CT and radiopharmacy for GE Healthcare (Waukesha, Wis). “Large patients are challenging to image with SPECT, especially regarding heart disease. In these cases, PET allows much better clinical image quality and improved diagnostic confidence.”
A Look at Usage
Specialized tracers?the radiopharmaceuticals that, upon injection, wend throughout the body and reveal potentially diseased sites?help determine the call for either PET or SPECT technology. Currently, PET procedures primarily use a glucose-based tracer called fluorine-18 deoxyglucose (FDG). Metabolically active areas like the heart, brain, and cancerous tissue absorb disproportionally high amounts of FDG’s glucose; its radioactive elements?positively charged electrons called positrons that collide from opposite directions?are picked up by the scanner. The result is 2-D or 3-D images displaying these “hot spots.”
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Instead of relying on one workhorse tracer, SPECT technology employs a variety of more traditional agents used in nuclear medicine, depending on the desired application. As opposed to PET’s collision-coursed positrons, SPECT tracers rely on a single bundle of gamma radiation to produce images; thus, the two machines require entirely different hardware. The differences are reflected in the price: PET scanners are around three times the cost of SPECT scanners.
The pricier machines (and studies) incorporate newer and more advanced technology. “PET has a much higher resolution as an imaging modality [than SPECT],” says Lionel Zuckier, MD, director of nuclear medicine and PET imaging at The University Hospital (Newark, NJ). “It’s also quantitative. In a SPECT scan, it’s very hard to say that this part of the body, for example, has two percent of what we injected. With PET, it’s much easier for us to [quantify this information].”
The quantitative element of PET allows physicians more accurate diagnoses, but achieving this accuracy takes time?up to 1 hour for a scan. “One of the factors you have to overcome is attenuation,” Zuckier says. “The problem is, deep in the body, there’s a higher likelihood that the photons exiting the body will be absorbed by overlying tissue. [Without attenuation correction], things deep in the body will appear less hot, and more peripheral things will appear more hot.”
Zuckier notes that attenuation correction can be achieved in different ways, but the advent of a PET/CT hybrid, which quickly calculates an attenuation map, has proven to be the most efficient. The result? In one fell swoop, the hybrid improved diagnostic accuracy, cut scan time in half, reduced patient motion, and increased throughput.
The SPECT/CT hybrid?whose introduction far predated PET/CT’s release in 2000?originally was developed to correct attenuation, improving diagnostic accuracy for its own applications. But this rather prosaic beginning for both hybrids truly undercuts their extraordinary potential. These machines?now supercharged with the latest technology?are poised to make such an impact on diagnostic imaging that, at some point, they will likely render their stand-alone cousins obsolete.
Hybrid Technology: The Best of Both Worlds
“I believe that in the future, most nuclear-medicine studies are going to use either PET/CT studies or SPECT/CT studies,” asserts Henry Royal, MD, associate director of nuclear medicine at Mallinckrodt Institute of Radiology (St Louis).
That seems to be the standard of enthusiasm for hybrids in the nuclear medicine community?and for good reason. The coupling of the physiologic information that PET and SPECT offer, along with the anatomical information that high-performance CT provides, guarantees a future?and a present, for that matter?rife with possibilities. And although SPECT hybrids have yet to create the same stir that their PET/CT cousins have caused, many expect that to change.
“The key benefits of combined modalities are improving the reader’s confidence and accuracy,” Rollo notes. “[With traditional PET or SPECT studies], the limited number of photons emitted from the area of abnormality provides a very low-level background that makes it difficult to anatomically localize the area. Adding CT helps determine the presence of that area of abnormality from an anatomic perspective … and categorize the likelihood of that representing disease.”
Royal concurs, adding, “For example, if you’re doing a PET study, and you see a local area of increased activity in the abdomen, that area could be normal if it were in a normal bowel. But if it were in a lymph node or a tumor mass, it would be abnormal. With just anatomic [CT] imaging, it’s difficult to tell by size alone if a lymph node is normal or abnormal. The combination of the two?seeing that it’s in a lymph node and it’s hypermetabolic?is the thing that gives you the accurate diagnosis.”
Also, he notes that the increased diagnostic accuracy of the hybrids offers a host of benefits, including the prevention of unneeded surgeries or other invasive procedures.
“One study1 on patients with lung cancer showed that with PET/CT, you can avoid futile surgery?surgery that isn’t going to help the patient,” Royal says. “There are two ways in which you can have futile surgery. One is that you perform the surgery and find out that the lesion was benign. In the second, you perform the surgery and discover the tumor has spread far more than you thought. [Hybrid] scans help decrease these futile surgeries.”
Beyond increasing physician confidence regarding disease diagnosis and staging, PET hybrids are playing a crucial role in determining a patient’s response to treatment, according to Rollo.
“Since PET is looking at the metabolic ability, it can indicate the presence of change anywhere from three to six months prior to that observed on CT,” he notes. “For example, you may have an area of abnormality shown on a CT and confirmed by a PET study. Upon applying therapy, the tumor on the CT many months later could appear to be the same relative size, whereas the PET study might show that the area of active tumor was reduced dramatically. The point is that with CT alone, you might make the guess that therapy was not working; whereas with [the hybrid], you have a far more sensitive indicator on the efficacy of the therapy on the basis of change and volume of metabolic activity.”
PET/CT technology is playing a critical role in guiding radiation therapy, Royal says. “[Traditionally], when determining what part of the body is to be treated with radiation, they’re going by the size of the mass and where the mass is located,” he explains. “The problem with this approach is that parts of the tumor are necrotic?not living. PET can tell you not only where the mass is, but also where the most accurately growing part of the mass is. That can change how your radiation therapy is performed.”
SPECT/CT technology is making its own contribution to radiation therapy, specifically for patients with prostate cancer, Rollo says. These studies use a radiotracer called ProstaScint (manufactured by Cytogen Corp of Princeton, NJ), he says, adding that PET’s FDG has proven ineffective for this type of cancer.
“With SPECT and CT combined, we are now able to identify evidence of recurring prostate cancer as small as 45 millimeters,” Rollo says. “In the past, absent that high accuracy, patients were treated with brachytherapy. In other words, radioactive seeds were placed in the pelvic region, and the beta radiation would kill not only the cancer but also the surrounding tissue, [potentially] causing incontinence or destruction of the bowel.
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| Both colon cancer scans shown here were captured with GE Healthcare’s Discovery PET/CT at the National Cancer Center in East Japan. The fused volume rendering of a PET/CT angiography (above left) provides vascular and metabolic visualization for surgical planning. In the zoomed view (above right), the surgeon is able to better understand the blood supply and vascular involvement of the tumor in advance of surgery. |
“[With the hybrid, we now can] direct intensity modulated radiation therapy?IMRT?to fire rifle shots directly at specific cancers,” he continues. “The result is that 100 percent of the patients treated have zero complications; whereas, in those treated with brachytherapy, the morbidity or complication rate is up around 85 percent. So the ability to add CT is dramatically changing the way we treat not only recurring cancer, but primary cancer in the prostate.”
In the past, hybrids have not incorporated state-of-the-art CT technology; that has changed. PET hybrids armed with 64-slice CT and 4-D gated technology are now available.
The additions to the CT half of the hybrid are significant. The high-volume, 64-slice scans increase speed, detail, and accuracy on hybrid studies. On the other hand, 4-D technology addresses problems that arise when imaging moving anatomy, such as the heart and lungs. Tumors, for example, can be imaged in 3-D, while the patient’s motions are tracked in the fourth dimension?time.
Piotr Maniawski, senior marketing manager of clinical applications for Philips Medical Systems (Cleveland), explains that while historically, CT scanners have been able to freeze phases of the respiratory cycle, the inability to determine the specific phase has required extra margins to the therapy volume to accommodate possible tumor motion. He says, “4-D imaging with respiratory gating allows you to understand the exact motion of the tumor throughout the cycle and plan therapy more accurately.”
SPECT hybrids have been especially slow to adopt up-to-date CT technology, likely accounting for their poor sales relative to PET hybrids, Rollo says. “Hybrid imaging in SPECT has been around for many years. The imaging system, however, was used only for attenuation correction and didn’t provide any of the diagnostic information that CT was capable of providing. The newer machines that allow a high level of diagnostic quality for localization are just being turned on. The first ones have been installed only in the last month or two,” he says.
SPECT hybrids make up about 10% of all SPECT sales in this country, according to Ron Chavez, nuclear medicine clinical product specialist for Philips Medical Systems (Milpitas, Calif). Alternately, Maniawski says that PET hybrids now account for about 95%?99% of all PET sales in the United States, and around 90% of PET sales worldwide.
Although the numbers might indicate a pervasive interest in PET hybrids, some in the nuclear medicine community believe the 5-year-old modality is currently underutilized. “As PET becomes more available, referring physicians must understand what the appropriate indications are for the studies,” Royal notes. He says that some patients are scanned with PET needlessly, while many others who could benefit are not being referred. “This is a generic problem in medicine, where there’s a lot of inertia. If whatever you did was good five years ago, it’s hard for people to change their views and say, ‘There’s something different I should be doing today,’ ” he adds.
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Siemens Medical’s Frey agrees, noting that acceptance of these new technologies includes varying degrees of re-education. “Societies are making an enormous effort to ensure that radiologists are properly trained to read nuclear images and that nuclear physicians are properly trained in reading cross-sectional, anatomical imaging. That was a big challenge when [the hybrids] were originally introduced,” he says. “[A related issue confronts] technologists: Different states require different regulations with respect to what training is required for technologists operating PET/CT scanners. In some states, you must have a CNMT [chief nuclear medicine technologist license]; in some states, just an RT; in some states, both; and in other states, neither. We’re working hard to ensure that education is broad, and certification requirements are clarified.”
What’s on the Horizon?
“One big area of interest in the nuclear medicine community is dementia and Alzheimer’s disease,” Zuckier says. Reimbursement for FDG PET scans now exists, he says, but approval is highly restricted and requires that a battery of other tests be performed first. The dementia also must be established, and the etiology is unknown.
Plaque-imaging tracers for the brain are currently in the works to address specific aspects of the disease, Royal says. He believes that these new agents, coupled with advancements in effective treatment for Alzheimer’s, should encourage more widespread coverage.
Maniawski adds, “From a cardiac perspective, PET offers the promise of absolute quantification of myocardial blood flow measurement, or coronary flow reserve measurement. That data will likely be combined with CT coronary angiography, presenting a full picture to the diagnosing physician.”
SPECT is just now adopting target-specific tracers for both diagnostic and therapeutic applications in oncology, according to Rollo. The recent advancements in hybrid technology were needed to complement these agents, he says, and the combination has opened the door to a host of advancements in this realm. “We now have 12 molecular imaging agents that are being evaluated in clinical trials that are target-specific,” he says. “Unlike [the FDG in] PET that will go to any cancer, these agents will go specifically to colon cancers, lung cancers, breast cancers, [etc].”
Rollo also explains that each of these tracers has a therapeutic counterpart added to the agent that will allow physicians to diagnose and treat patients, potentially replacing chemotherapy as an alternative. “[To use these tracers], we need the accuracy of [the recent hybrids] to accurately define the presence of the disease and determine whether the therapy is working,” he says.
Target-specific tracers for cardiac applications also are coming into play for the SPECT hybrids, he adds. “One agent allows us to determine, within 30 minutes of the time a patient experiences chest pain, whether or not there is ischemia. Right now, it can take 12 to 14 hours to determine the probable cause of the event. We believe [that with this capability,] we’ll save many lives and will dramatically change the therapy.”
PET tracers are inherently more difficult to develop than SPECT tracers, according to Zuckier. “Radiopharmaceuticals that incorporate positron radionuclides [that PET requires] tend to be very short-lived and are cyclotron-produced,” he notes. “So, unless you have a cyclotron on-site, you can’t use a lot of the shorter-lived tracers.” Zuckier says that FDG has, at 110 minutes, a long half-life for positrons, increasing its relative practicality.
He adds that one PET tracer being developed, 18F-fluoro-L-thymidine (commonly known as 18F-FLT), which is an analog of thymidine, reports on the activity of DNA proliferation, and it should be useful in tumor evaluation. He notes that while the chemistry will drive the business, the relatively short half-life and high expense of many PET tracers could somewhat inhibit future development.
Regardless, PET’s exceptional FDG should carry the modality for a good while. The tracer is considered a blockbuster in the industry, according to GE Healthcare’s Kuppusamy, because of its versatility and effectiveness. A PET tracer called fluorocholine is in the works to address one of the few applications in oncology that FDG cannot: prostate cancer. However, its release is 3?5 years away, Kuppusamy notes.
“It’s an interesting time, from a medical imaging perspective,” Frey says, “because all imaging modalities are going through a great imaging renaissance?CT, MR, PET. Hybrid imaging presents an enormously dynamic environment, as both [entities] are changing at the same time.”
This dynamism seems to be increasing the potential of hybrid imaging exponentially. “Increasing diagnostic accuracy, increasing the physician’s confidence level, and determining the most appropriate therapy are the reasons we believe PET/CT and SPECT/CT will completely change not only the way physicians practice, but also the clinical value of the procedures,” Rollo says.
Royal agrees, adding, “Advancements in imaging are heading toward focusing on better defining one’s physiology rather than one’s anatomy. The history of medicine has been very anatomically based. I think future decisions are going to be made more on the physiology of the patient’s particular problem.”
Mark Dye, RT, is a contributing writer for Medical Imaging.
References
- Verboom P, Van Tinteren H, Hoekstra O, et al. Cost effectiveness of FDG-PET in staging non-small cell lung cancer: the plus study. Eur J Nucl Med Mol Imaging . 2003;30(11):1444?1449.
