April 26, 2010

PET Myocardial Perfusion Imaging — A Promising, Though Expensive, Alternative to Stress Tests
By Beth W. Orenstein
For The Record
Vol. 22 No. 8 P. 24

Physicians at University Hospitals Case Medical Center of Cleveland were using PET to image beating hearts before the technetium 99m (Tc 99m) shortage required many facilities to seek alternatives to nuclear stress testing. James O’Donnell, MD, director of the division of nuclear medicine and PET at University Hospitals, believes PET myocardial perfusion scanning is the superior technology anyway and that the shortage of Tc 99m will allow more physicians to realize that.

“The specialty is moving toward more and more PET scanning in general, and cardiac PET scanning in particular, for a variety of reasons,” he says. “The shortage of technetium is giving PET scanning a boost because if it’s harder and harder to obtain technetium, then there’s more pressure to move to PET scanning which, while more expensive, has a number of advantages.” Indeed, PET cardiac studies provide such clear images of the heart, even in difficult patients, that O’Donnell predicts “in five years or so, we’re going to be doing almost entirely PET scanning for nuclear cardiology studies.”

Mo 99 Shortage
The Chalk River nuclear reactor in Ontario, Canada, which normally supplies about 50% of the world’s molybdenum 99 (Mo 99) used for diagnostic medical imaging studies, has been out of service since May 2009 due to a water leak and was still shut down when this issue went to press. Limited Mo 99 supply means reduced Tc 99m generator production.

Bracco Diagnostics Inc manufactures rubidium Rb 82, the only FDA-approved generator-based PET myocardial perfusion agent used for detecting coronary artery disease, selling it under the trade name CardioGen-82. The agent is produced from an Sr-82 generator, which has a 28-day half-life and is available on demand; it is not reliant on Mo 99 supply.

In light of the shortages caused when the Chalk River nuclear reactor went down, Bracco sent a letter to healthcare professionals encouraging them to consider CardioGen-82 as an alternative. In the letter, Bracco reported that CardioGen-82 had experienced double-digit, year-over-year growth during the previous five years and echoed O’Donnell’s prediction that it is on its way to becoming the standard for managing patients with coronary artery disease.

Some who have been using rubidium for myocardial perfusion imaging (MPI) even before the shortage say they find it superior to nuclear imaging with Tc 99m or thallium for coronary artery disease. Thallium had been used until Tc 99m agents came along, and some have begun utilizing it again due to the Mo 99 shortage.

Difficult Cases
Rubidium users say it is particularly helpful in difficult cases (eg, patients who are obese or have diabetes and women with large breasts or breast implants). Images are not only superior in quality to technetium studies but also faster to obtain. A PET scan takes about 35 to 40 minutes—the scan itself is 10 minutes—compared with a SPECT study that takes three to four hours. Many believe the imaging field would be moving faster toward PET MPI were it not for the high cost and the inability to conduct exercise-induced stress testing.

Mimi Guarneri, MD, FACC, medical director and founder of the Scripps Center for Integrative Medicine in La Jolla, Calif., says her practice started using PET imaging for heart disease in 2004, long before the current shortage. “We chose to bring it not because of a shortage,” she says, “but because the rubidium is a very potent isotope. It has a kiloelectron volt of 511, so it penetrates the chest wall in such a way that your patient can be obese, your patient can have large breasts or breast implants, and you still will have beautiful clear images. It provides the clearest images, especially in complicated patients who frequently have artifacts from obesity or from breast tissue or breast implants. For me personally, it is the ideal imaging modality for women and particularly for those patients who are overweight.” Guarneri says research confirms that CardioGen-82 PET offers imagers interpretive certainty of 96% vs. SPECT, which is 82%.

O’Donnell adds elderly patients with small hearts to the list of those who do better with PET MPI than SPECT. “Because the image resolution is higher with the PET scanner, you can see things better,” he says. Also, PET MPI is useful with patients who have diabetes who are more likely to develop coronary artery disease, he notes. “But before they develop large-vessel disease in their coronary arteries, they have small-vessel disease involving those tiny little arteries that penetrate down into the muscle, and we can see that with PET,” he says. PET MPI provides quantitative data, “so we’re able to see any segment of the heart that is not perfusing.”

Clearer Images
Guarneri believes the movement toward PET MPI is often a matter of education. “We have found with the cardiologists here that once they see the PET cardiac images, their whole attitude changes. They start to prefer PET because it’s so much clearer,” she explains.

While PET MPI is covered by Medicare and some private insurers, cost remains an issue, says Guarneri, whose center spends $30,000 per month for its rubidium generator. She expects insurance companies that don’t yet approve the procedure will eventually. “It just takes time for insurance companies to catch on,” she notes.

O’Donnell says sometimes it’s a matter of getting preapproval from the insurance companies. PET MPI is not considered to be research or experimental, he says, since it is clinically validated.

One limitation with PET vs. SPECT is that the short half-life of rubidium makes exercise stress testing challenging, according to Marcelo Fernando Di Carli, MD, chief of nuclear medicine and codirector of cardiovascular imaging at Brigham and Women’s Hospital in Boston, which started a PET program in 2003. Being able to do stress testing induced by exercise is important, Di Carli says, especially if patients present because of exertional chest pain. In those cases, he says, “You would like to be able to reproduce the symptom by having them on a treadmill. This helps differentiate between cardiac and noncardiac chest pain, provides important information about exercise capacity relevant for risk prediction, and gives physicians useful information for guiding subsequent management. It is difficult to extrapolate this information from pharmacologic stress tests.”

Treadmill Studies
Robert Kovac, Bracco’s product manager for nuclear cardiology, points out that many patients needing perfusion studies are unable to exercise on a treadmill. “Data shows that 48% to 50% of studies done in nuclear cardiology are pharmacological stress, largely because patients are unable to walk on a treadmill.” Di Carli also says about one third of patients are not good candidates for exercise stress testing, “and so for those patients you have no other options than pharmacological stress.”

Obviously, imaging facilities need a PET scanner to perform PET MPI. Users say that’s no longer an issue for most facilities. “Today, PET is becoming standard technology for cancer patients, and many major institutions have a PET scanner,” Guarneri says.

Kovac adds that many hospitals, especially larger ones, have a PET scanner and cardiac software capabilities for cardiac PET. “The numbers I have heard is that most places do four oncology studies a day, and so they have available time to shift over to cardiac patients,” he says. Facilities would need to maintain due diligence and determine whether patient volume exists to support cardiac PET imaging, Kovac says, because there is a large fixed monthly cost for a rubidium generator.

At some institutions, the cardiac PET scans are read by both nuclear medicine physicians and nuclear cardiologists, Kovac says.

Coronary Disease Revolution
O’Donnell believes using PET for cardiac imaging coincides nicely with the revolution taking place in the diagnosis and treatment of coronary artery disease. “We used to think that coronary artery disease was caused by cholesterol,” he explains. “Now we know that coronary artery disease is a systemic disease. It’s generalized inflammation that causes a gradual buildup of plaque in the patients’ arteries and that most heart attacks are not caused by the big blockages. Most heart attacks are caused by the rupture of these small arteries that then cause the blood to clot in that area. When we do scanning or coronary angiograms and find some narrowing of an artery, that’s pretty late in the disease, and the patient probably has a lot of other plaque disease that may not be narrowing the big arteries but they’re likely to be the culprits for heart attacks. If a patient is found to have a high-grade blockage, you have to deal with it, but coronary artery disease starts a lot sooner than that, and thus it needs to be detected earlier.”

PET imaging allows physicians to detect the buildup of plaque in the smaller arteries long before a big blockage is detected, O’Donnell says. If disease is detected earlier and treated with medications to lower cholesterol, blood sugar, and hypertension, a patient could be saved from having a heart attack or undergoing bypass surgery, he says.

Ongoing Issue
Guarneri expects the shortage of radioisotopes to remain a problem for some time. The Petten reactor in the Netherlands, the world’s other major supplier of Mo 99, is in need of regular maintenance and expected to go offline for some time. If things go well, the Chalk River reactor will be back up by that point, which the Canadian government recently promised would be the case.

Meanwhile, in November 2009, the House of Representatives approved a bill to help fund production of Mo 99 in the United States. Still, Guarneri believes the reactors’ perilous and costly status is impetus for researchers to continue looking for new isotopes that will allow for less attenuation correction, less artifact, and shorter half-life.

“Right now, PET rubidium imaging is the one option and it’s an option with very high sensitivity and specificity,” she says, “but I think there are other options in the research phase right now that will eventually change the playing field.”

— Beth W. Orenstein is a freelance medical writer in Northampton, Pa.