Positron emission tomography (PET) is best known for providing unique and clinically vital information that is not available through other diagnostic imaging modalities. Ongoing advances in PET technology has medical researchers and physicians excited about its growth and potential in many areas of medicine.

Cancer Staging and Treatment
The primary use of PET today seems to be in staging cancer growth and treatment. According to Deepak Malhotra, director of PET Marketing at Philips Nuclear Medicine (Milpitas, Calif), 90% of the procedures that PET is utilized for are oncology (diagnosis, staging, and restaging); 5% of the procedures are cardiology related, such as cardiac viability and perfusion studies; and 5% are neurological procedures.

PET has proven to be very efficient in staging a variety of cancers, such as esophageal, head, neck, and colorectal.

The patient scanned for the PET image left (courtesy of neo-pet LLC and Williams County Community Hospital of Bryan, Ohio) suffers from Pancoast-type lung cancer with unexpected metastases in the right and left adrenal glands as well as the lower rib cage. The patient in the PET image on the right (courtesy of neo-pet LLC and Akron General Hospital of Akron, Ohio) has a history of colon cancer and liver metastases and has had chemotherapy; however, the patient still shows three clear metasteses in the liver, indicating poor response to treatment.

“PET provides metabolic information that isn’t provided by CT or MRI,” explains Floro Miraldi, ScD, MD, CEO and founder of neo-pet LLC (Oakwood Village, Ohio). “This metabolic information helps identify malignant tissue earlier and in unexpected locations. Most studies indicate that PET studies change the patient treatment plan in roughly 30% of the times it’s used. PET can be used to avoid some invasive procedures due to its high sensitivity. If it’s negative on PET, it’s unlikely to be a malignant process. PET is also extremely valuable in detecting cancer recurrences when anatomical changes, like scar tissue from surgery, make conclusive interpretations from CT or MRI very difficult.”

Also, PET has proven to be an efficient and invaluable tool in restaging patients.

“Lymphoma cases have a long-term therapy regimen, so PET can be used as an indicator of how well therapy is going and as a restaging tool to let doctors know if therapy needs to be modified,” says Steve Hayles, national PET specialist for Alliance Imaging (Anaheim, Calif).

PET usage has grown in cancer staging and diagnosis since it received Medicare reimbursement approval in 1998. Reimbursement is limited in other areas of PET application, such as in neurology. According to the results of a recently released study, Blue Skies or Storm Clouds Ahead for Cancer’s PET?, by Marketing Relevance LLC (Knoxville, Tenn), although financial reimbursement exists for PET scanning, a large number of surveyed physicians were not aware of the PET reimbursement standards, leading to potential underutilization.

“Oncologists treating cancer are just beginning to understand the power of PET,” says Jeff Kao, general manager of functional imaging at GE Healthcare (Waukesha, Wis). “It is obviously one of the most exciting modalities in the marketplace now. There is a huge movement to actually quantify PET so patients receive better care.”

The Biograph Duo PET/CT scanner from Siemens Medical Solutions (left) gives Molecular Imaging Corp the ability to offer physicians diagnostic information, including both metabolic and anatomical, in one co-registered image.

PET is highly effective in providing insight in how to treat a patient—with chemotherapy, radiation, surgery, or all three. The staging information that PET provides enables physicians to determine if the disease is localized or disseminated.

“PET looks at the biology of cells that are taking in more or less glucose than normal cells. It gives biological information instead of structural information,” explains Mark S. Rhoads, president of Marketing Relevance. “It can diagnose patients with Alzheimer’s disease much earlier than otherwise by using symptoms at an early stage. PET can diagnose it 3 to 4 years earlier, which allows the patient to try different drugs that are on the market and to participate in clinical trials as well.”

Pulmonologists and oncologists are the biggest referrers for PET, which is unsurpassed for distant metastasis detection, according to neo-pet’s Miraldi, who points out that cardiologists use PET more frequently for cardiac viability studies because it can differentiate living tissue from a scar.

“PET has been used as a research tool for about 20 years. Only in the past 5 years has it become a widespread clinical tool, when broader Medicare coverage was offered,” notes Hayles of Alliance Imaging.

More education is needed to provide the general physician population with specific clinical reasons as to why molecular imaging is superior to using only anatomical imaging procedures in the detection of a range of diseases, according to Paul J. Crowe, CEO of Molecular Imaging Corp (San Diego). The introduction of the combined PET/CT modalities will facilitate an accelerated adoption of this powerful diagnostic procedure by mainstream medicine, he adds.

“The departure from diagnosing disease from symptoms, utilizing anatomical imaging procedures, and subsequently treating anatomical areas of disease is changing to one where physicians begin by analyzing biochemical changes first, then diagnose the disorder, and then treat it at the molecular level,” Crowe explains. “It’s where medicine is headed, and some clinicians are always the first movers. As with MRI in the early 1980s, only neurology specialists involved in central nervous system disorders used this emerging technology. Today, a single specialist group—oncologists—is really using molecular imaging for the benefit of their patients. Like MRI, it will take time to educate more specialists.”

As PET procedure volume increases, educational awareness needs more focus on specific disciplines in medicine as well as elevating public exposure. Raymond Wtulich, marketing product manager for Hitachi Medical Systems America (HMSA of Twinsburg, Ohio), says that “reimbursable PET indications have recently been added to the National Comprehensive Cancer Network [NCCN] Clinical Practice Guidelines in Oncology. The NCCN is a network of 19 leading cancer centers in the United States that develop evidence-based guidelines in oncology. These guidelines’ panels combine a thorough review of the evidence with expert opinion in developing the most up-to-date reference information available in oncology today.”

HMSA has combined clinical case studies along with the appropriate practice guidelines for customer marketing to oncologists. “Our customers have told us that these clinical tools have been very successful, as many oncologists use the NCCN Guidelines in their patient management,” Wtulich adds. [Guidelines can be downloaded from the NCCN Web site (www.nccn.org).]

Rhoads believes that a focus on improving the technology, to the deficit of educating the referring physician, might limit the overall use of PET.

“Manufacturers are focusing on the PET technology and the equipment instead of educating referring physicians,” he says. “Considering the significant opportunities of using PET in improving cancer treatment, physicians, and those who PET is reimbursed for, the industry is apparently not focused on applying itself to referring physicians.”

Besides the importance of educating referring physicians about PET’s applications and advantages, it is also crucial that physicians are well trained in reading the images.

“If PET images are misread, physicians will lose confidence in this new technology,” Rhoads says. “The interpretation of the image is very important because referring physicians can’t read it themselves. PET scans require extensive training in order to read. Radiation oncologists are trained to read CT scans in medical school, but they are not trained to read PET scans.” This is problematic for the growth in the number of PET procedures.

GE Healthcare’s Kao agrees that PET education needs to continue: “We are still trying to educate the marketplace about PET’s role in cancer diagnosis.”

Combining CT’s Strengths
There are more dedicated PET scanners worldwide than PET/CT, although that will change rapidly, according to Jonathan Frey, director of PET marketing in the nuclear medicine division of Siemens Medical Solutions (Knoxville, Tenn).

“Siemens’ PET/CT together offers three key new technologies,” Frey explains. “It improves the spatial resolution of PET enormously. We just introduced 4.5-mm spatial resolution. PET/CT also provides an improvement in count-rate performance in PET technology. It’s now more than 50% better than what it has been. PET/CT also enables multidimensional imaging. With 4-D imaging, we are able to track motion better within the patient, either cardiac or respiratory motion. And with PET/CT, one is able to distinguish normal uptake from abnormal uptake, especially in the abdomen and intestines.”

Alliance Imaging provides the power of PET scanning (shown here) without the capital investment or financial risk to new customers.

He adds that PET/CT scans are easier to read for those without PET training, because CT enhances images and makes them easier to read. The fusion scan also reduces patient scanning time. A PET scan typically takes 60 minutes, while a PET/CT takes just 15 minutes.

PET/CT fusion provides physicians with the ability to see a lesion with PET technology as well as to localize the lesion with CT technology, according to Malhotra of Philips.

“In 1 year, the market has flipped in the number of PET/CT units sold versus the number of PET units,” he explains. “There is growing evidence that PET/CT provides significantly better diagnosis versus PET alone and CT alone.”

Molecular Imaging’s Crowe agrees, adding, “The combined PET/CT cameras are the newest wave. PET/CT has taken over as the number one imaging modality combining anatomical structure and metabolic information. The combination of these two technologies offers superb resolution and sensitivity. All types of physicians have, over the past 3 decades, gained a deep understanding of CT imaging; because of that, the combination systems provide a unique platform for learning metabolic imaging faster and more efficiently than if working with just a stand-alone PET system.”

In some circumstances, using PET and CT together can be helpful to better localize PET data.

“PET/CT has the clearest value to radiation oncologists who are planning radiation therapy. Fusing the PET data with their simulation CT can lead to more efficient treatments,” explains neo-pet’s Miraldi. “Due to the different physics of the machines, PET and CT can be difficult to register in many situations. A patient’s voluntary or involuntary movement, including breathing and organ movement, can cause difficulties in hardware fusion. Software fusion can avoid some of these problems by providing the flexibility to fuse only a small region of interest.”

Irving Weinberg, MD, president of Naviscan PET Systems (Rockville, Md), adds that the current generation of whole-body PET scanners “do not have the spatial resolution” to visualize early cancers, such as ductal carcinoma in situ of the breast. Although intense efforts are underway to improve the spatial resolution of whole-body PET, Naviscan’s PEM Flex device was recently cleared by the FDA as a high-resolution PET scanner to address these concerns.

Weinberg adds that current whole-body PET scanners do not have the count efficiency to collect data in a short enough time to direct a biopsy, so additional modalities—such as CT—are integrated with the PET image. Naviscan’s PET scanner is designed to image small body parts with high efficiency and achieve short scan times. The PEM Flex device integrates high resolution PET images with other digital anatomic imaging modalities (eg, spot digital mammograms).

The Journal of Nuclear Medicine featured a recent supplement¹ on the issue of PET/CT. “The article indicates there are clear benefits of having the anatomical data of CT to use with the metabolic data from PET, but it questions whether enough scientific evidence exists to promote one type of fusion—visual, hardware, or software—over another,” adds Miraldi. “One of our internal studies indicated that PET/CT fusion might only be needed in 5% of all PET scans. Further, PET/CT is reimbursed the same as a PET scan, which can lead to significant financial constraints.”

A different study² states that on the basis of PET findings alone, 45 lesions were considered benign, 39 were considered equivocal, and 71 were considered malignant. With PET/CT, the fraction of equivocal lesions decreased by 53%, from 39 of 155 to 18 of 157 (P<0.01). PET/CT had a higher accuracy of depicting cancer than did PET (96% versus 90%, P=0.03). Six proved malignancies were missed with PET, but only one was missed with PET/CT. The PET/CT findings altered the care for 12 (18%) of 68 patients.

“PET/CT shows the viability of tissue, provides anatomical information about cell structure and what’s going on inside the patient’s body,” states Kao of GE Healthcare. “It also provides artery and tissue images. We can gain functional and anatomical information from both PET and CT, and the software puts it all together.”

He also sees PET technology moving into respiratory gating and treatment as well as neurology. With respiratory gating, the patient breathes normally while the physician gets images that are not degraded by motion. This could enable them to detect smaller lesions in the lung.

“Traditionally, an MRI looks at the brain activity and tissue,” Kao explains. “Many studies show that PET/CT is more sensitive.”

Weinberg adds, “Clinically, future PET systems will need better spatial resolution, biopsy capability, correlation with other modalities, such as ultrasound and MRI.”

Other Advancements
A huge new field of exploring drugs and agents that can be used to look at cellular growth inside the brain is emerging, thanks to PET/CT’s higher resolution and sensitivity, Kao explains, adding, “PET is more sensitive and specific in many neurological studies and is opening up ways to study the brain in ways we never imagined years ago.”

William Stein, MD, is part of Hematology and Oncology Specialists LLC (New Orleans) and a staff member at East Jefferson General Hospital (Metairie, La). Stein is very enthusiastic about PET’s diagnostic abilities and future growth applications. He is researching the usefulness of positron emission mammography (PEM) with the Naviscan PEM Flex PET scanner in detecting breast cancer.

“The PEM Flex is very accurate at finding tumors,” he explains. “There are essentially no false-positives. We think this is going to be the biggest advance in the detection of breast cancers. It will be revolutionary to the practice of oncology because it is very accurate for evaluation and staging. We are absolutely beside ourselves thus far. PEM is as much an advance in breast diagnosis as PET scans were for the rest of the body. PEM will probably eliminate some needless surgery for breast lesions and change our surgical approach to others.” Stein anticipates that PEM will be available in clinical practice very soon.

Multidimensional aspects of PET also are being explored, up to 5-D. Wider scanners are being developed to accommodate larger patients, and researchers are exploring ways to improve image quality.

“As medicine gets more sophisticated in its use of molecular targeting, physicians will need better tools for prevention, diagnosis, and therapy. PET has several strong advantages over other biochemical imaging modalities, especially when the PET device can be tailored to specific clinical missions. In the past, access to PET was limited by the availability of positron-emitting radiotracers. The PET radiopharmacy market is still in its early stages, with only one radiotracer, FDG [fludeoxyglucose F 18], approved for wide clinical use,” Weinberg explains.

Another driver of PET acceptance will be marketing to subspecialties other than radiologists. Interventional suites are used more by cardiologists than radiologists these days, even though the basic techniques of interventional cardiologists were invented by radiologists, according to Weinberg. Urologists and surgeons currently use ultrasound devices; however, PET-based or combination PET/anatomic devices also could be tailored for use by surgeons if the clinical results warranted such applications. The marriage of PET technology to minimally invasive therapy could be the breakthrough application that will achieve truly wide use of PET, he believes.

PET/CT equipment now incorporates the latest generation of gamma detectors, such as lutetium oxyorthosilicate (LSO) crystals. New radiopharmaceuticals constantly are being developed that increase the indications for use of PET, Miraldi explains.

“Most of the systems we employ have image co-registration software, allowing our customers to co-register CT/PET/MRI imaging procedures,” says Crowe of Molecular Imaging. “We are now upgrading our 25-plus systems to the newer combination cameras to continue to offer our customers and partners the latest generation molecular imaging technology. The major companies leading the charge in developing the combination cameras are Siemens, GE Healthcare, CTI, and Philips. These companies have developed robust technologies blending their respective CT and molecular imaging platforms. Features differ from one vendor to another, and the buyer has to decide which product or vendor best meets their specific needs.”

Miraldi also has words of advice for facilities considering adding PET. “PET programs can be challenging to set up. Reimbursement for PET is complicated, and many referring physicians need to better understand how PET could be useful in their practice,” he explains. “Many hospitals and imaging centers find it very valuable to have an experienced partner to help them develop their PET program.”

Laura Gater is a contributing writer for Medical Imaging.

References
1. Vogel V, Oyen W, Barentsz J, Kaanders J, Corstens, F. PET/CT: Panacea, redundancy, or something in between? J Nucl Med. 2004; 45:15S-24S.
2. Schoder H, Yeung HW, Gonen M, Kraus D, Larson SM. Head and neck cancer: clinical usefulness and accuracy of PET/CT image fusion. Radiology. 2004; 231(1):65-72.