More than 25 years after its introduction, positron emission tomography (PET) is finally coming into its own as a cutting-edge, practical diagnostic tool. Once rare outside of research centers and the occasional university hospital, PET today is proliferating at hospitals and medical centers across the country.
As recently as 1997, approximately 50 healthcare facilities in the United States had PET scanners installed. That number has escalated to approximately 180, with new sites being added almost monthly.
“I think PET has carved out its niche and this whole area of metabolic imaging is going to grow considerably,” says Aaron Hazzard, vice president and COO of Jewish Hospital (Louisville, Ky.).
Jewish Hospital added mobile PET services in February and has seen a steady demand for scanner time. The hospital has the scanner on-site two or three days a week, performing six scans per day.
“[PET] is something that has truly demonstrated its value to the field,” Hazzard says.
Taking off
When PET scanners were first developed in 1974, they were seen as a research tool to study brain and heart function. Unlike CT and MRI systems, which look at biological structure, PET images allow physicians to look at metabolic functioning.
“CT looks at anatomy and abnormalities in anatomy, but it doesn’t really tell you the characteristics of the abnormality,” explains Val J. Lowe, M.D., a PET imaging specialist at the Mayo Clinic (Rochester, Minn.). “PET tells you about the function of the abnormality, how it’s metabolizing.”
Advancements in the design of scanners and software development that allow for whole-body scanning increased PET’s clinical applications, but the cost of installing scanners and related equipment, coupled with a lack of reimbursement sources, prevented much growth beyond research fields.
“Prior to the last couple of years, there was limited private carrier reimbursement around the country for PET, but it was not widespread and not guaranteed,” explains Jennifer Keppler, executive director for the Institute for Clinical PET (Foothill Ranch, Calif.). “In the last couple of years, we’ve started to see Medicare approving certain types of procedures and continuing to expand that approval. Hospitals are perceiving that the risk of getting involved in PET is much less now that there is reimbursement guaranteed for it.”
In January 1998, the Health Care Financing Administration (HCFA) approved Medicare payment for PET for the diagnosis of solitary pulmonary nodule and for the diagnosis and staging of non-small cell lung cancer. Eighteen months later, HCFA added payment approval for the staging and follow-up of Hodgkin’s and non-Hodgkin’s lymphoma, melanoma, and recurrent colorectal cancer.
Additional oncology applications currently are under consideration, including evaluation of malignancies for breast, ovarian, head and neck and gastric cancers, as well as expansion of coverage of lung cancer and colorectal cancer.
HCFA also is evaluating the use of PET in examining brain tumors, epilepsy, dementia, Alzheimer’s disease and myocardial viability.
Expanding applications
With the first payment hurdles cleared, support services developed that made installing a scanner and offering services to patients easier than ever.
The scanner itself is only half the PET equation. Scans require radiopharmaceuticals to trace metabolic function, the most widely used of which is fluorodeoxyglucose (FDG) – a form of glucose with a short half-life that is easily metabolized by the body.
FDG’s short half-life means it cannot be stored, so until recently, installation of a PET scanner also required installation of a cyclotron to manufacture FDG. A typical cyclotron weighs 35 tons, requires 500 sq. ft. of space and can cost an estimated $1.5 to $2 million.
New companies, however, have begun building cyclotrons around the country, offering FDG and other radiopharmaceuticals to medical facilities on an as-needed basis. Instead of building their own cyclotrons, hospitals order FDG 24 hours prior to a scan. FDG then is delivered to the doorstep by truck or air freight.
One FDG supplier is P.E.T.Net Pharmaceutical Services Inc. (Knoxville, Tenn.), which has experienced 80 percent growth since opening its doors in 1996. By the end of this year, P.E.T.Net will have 25 cyclotrons in operation around the U.S. The company expects to have a total of 50 cyclotrons in place by the end of 2002.
The Biomedical Research Foundation (Shreveport, La.) has a cyclotron in place and hopes to market isotopes to other facilities in the future.
Eastern Isotopes (Winchester, Va.) has two cyclotron facilities serving Virginia, Maryland, Pennsylvania, Washington, D.C., New York, Missouri, Ohio, Indiana and West Virginia. The company is looking to open a new cyclotron in southern California this year.
International Isotopes Inc. (I3 of Denton, Texas) acquired the linear accelerator (linac) from the defunct U.S. Superconducting Super Collider project and constructed its facility in Denton, which supplies a variety of isotopes for PET and other medical uses. I3 plans to establish other linac facilities with overseas partners.
“The proliferation of FDG centers makes it more competitive [to do PET scans],” says Jewish Hospital’s Hazzard. “I know we have seen the price [of FDG] come down. Also, it gives us a number of sites to choose from, so that we aren’t relying on just one source. We have received FDG from both Chicago and Nashville.”
Hazzard estimates the price his hospital pays for FDG has decreased 20 to 25 percent in the last few years. The current list price of a dose of FDG is $750, but the price healthcare providers actually pay is negotiable.
New equipment options also have spurred PET’s growth. Mobile scanners make it easier for hospitals to ease into offering PET services without taking on a large financial risk. (See sidebar on page 47.)
In addition to dedicated PET equipment, recent developments allow other nuclear medicine equipment to add PET capabilities. Some single photon emission computed tomography (SPECT) cameras, already in place at many facilities, can be upgraded to perform PET scans. Development of lower-cost gamma cameras with PET capability has put PET in the reach of many more institutions.
The cost of SPECT gamma cameras ranges from $205,000 to $490,000. Coincidence imaging technology to perform PET scans increases the cost by $200,000 to $310,000, which still is below the cost of a dedicated PET scanner.
Information fuels growth
As more scans are done, more information about PET’s effectiveness and cost-effectiveness is available, which, in turn, fuels additional payment approvals and more growth.
The primary use for PET, at this point, is in the detection of cancer and as a way to monitor treatment of cancer. Tumor cells absorb glucose at an accelerated rate. When FDG is injected, the PET scan shows the rate of glucose absorption. Tissue may appear normal, but a PET scan can show abnormal absorption rates, indicating the presence of tumor cells before the tumor is evident on a CT scan. Likewise, PET allows physicians to determine if a tumor is malignant or benign without a biopsy, potentially preventing unnecessary surgery. PET tracks the course of treatment by demonstrating the tumor’s response to therapy, such as chemotherapy or radiation, allowing fine-tuning of therapy during its course.
The cost of a dedicated PET scanner averages $1.5 to $2 million. Reimbursement for PET services generally ranges between $1,980 and $2,400 per scan. Studies have shown that over the course of treatment for recurrent colorectal cancer, the use of PET can save between $5,423 and $32,123 per patient, primarily by eliminating unnecessary surgery. In studies of lung cancer patients, the use of PET saved $1,154 per patient in lung cancer mediastinal staging.1
Promising developments
In addition to its value in oncology, PET shows promise for the diagnosis and treatment of a variety of other diseases. For instance, PET scans with FDG can show neurological patterns characteristic of Alzheimer’s disease before standard neurological testing would show evidence of the disease. With new Alzheimer’s treatments being developed, the use of PET could be valuable for early intervention.
At Jewish Hospital, Hazzard says that, in addition to oncologists, thoracic and vascular surgeons, pulmonologists and hematologists utilize the PET scanner. PET can measure the function of heart tissue, helping to identify heart damage.
In addition, the development of new radiopharmaceuticals continues to expand the applications of PET. Mayo’s Lowe estimates that hundreds of these tracers are now being developed.
Newer radiopharmaceuticals may offer faster absorption times, allowing for quicker scans and, ultimately, more scans per day. Currently, the absorption time for FDG is approximately 45 minutes, allowing a PET center to perform six to eight scans per day. Newer compounds could allow patients to be scanned in as few as five minutes after the compound is injected.
Newer radiopharmaceuticals also show promise for the study of new diseases. “Some of the newer compounds are opening up new organ systems to PET,” says Mark Rhoads, president and CEO of P.E.T. Net Pharmaceutical Services. “For instance, there are about 5 million patients in the U.S. who have non-alcoholic steatohepatitis (NASH). There are a lot of pharmaceutical companies looking for treatments for NASH, but previously there was no good way to diagnose NASH and track treatment progress.” PET offers a diagnostic and tracking tool.
Prostate cancer has proven difficult to diagnose using FDG, which tends to spill into the bladder, obscuring the prostate from view. New radiopharmaceuticals are not excreted in the bladder, thus allowing a clearer view of the prostate.
PET scans with fluorodopa (F-DOPA), a radioactive form of dopamine, can measure dopamine uptake in the brain, which could be valuable for diagnosing various movement disorders, such as Parkinson’s disease and Huntington’s disease and determining the appropriate therapy. This same compound also may help in the diagnosis and treatment of depression.
“Probably the thing that’s capturing the most interest right now is the possibility that we can image gene therapy,” says Lowe.
In gene therapy, a disabled virus transports the desired genes to cells in the body. The aim is to replace missing or flawed genes in diseased cells with healthy genes.
“You can devise ways to use PET to see if your therapy has been successful,” Lowe adds. “There are tracers that have been developed that would essentially ‘light up’ in the area, if your gene therapy has been successful. That’s something researchers are very excited about.”
New equipment also promises to extend the application of PET. The next generation of scanners will combine PET and CT. “You’ll have the anatomy and the function on a patient in one scan,” explains Lowe. “One advantage is you’ll know exactly where the functional information is on the anatomical image. This will be a great help to surgeons, who can know exactly where to operate to remove the abnormality. It opens up new opportunities for biopsy.”
The American Cancer Society estimates that approximately 1.3 million people are diagnosed with cancer each year. Add to that the 1.5 million people who suffer heart attacks, the 4 million people with symptoms of dementia and the millions more with movement disorders and the potential for growth of PET becomes clear. From an expensive research tool, PET has grown to be a valuable weapon in the fight against disease.
“We’re all trying to detect disease earlier, so we can treat it at its earliest stage,” Hazzard says. “With PET, you can have a higher likelihood of promoting cures instead of just remissions.” 
1 Valk, Peter E., Pounds, Thomas R., Tesar, Ruth D., Hopkins, Donald M., and Haseman, Michael K., (1996) Cost-Effectiveness of PET Imaging in Clinical Oncology. Nuclear Medicine & Biology, Vol. 23, pp. 737-743.
