Time for a New Normal in Nuclear Cardiology?

Spurred by the isotope shortage, there is renewed interest in cardiac PET vs. cardiac SPECT for MPI
April Mann, BA, CNMT, NCT, RT(N)


December 6, 2010
Hartford Hospital performs about 1,000 CardioGen-82 PET MPI scans per year. Its PET/CT camera is a GE Discovery LS four-slice.

As production of molybdenum-99 returns to normal with the Canadian Chalk River Laboratories reactor back online and the supply of 99m-technetium stabilizes, the nuclear cardiology community is anxiously waiting to see if procedure volumes will rebound.

However, before the technetium isotope shortage began 15 months ago, nuclear cardiology was already starting to experience a decline in single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) procedure volumes due to the maturity of the modality, growing scrutiny and controversy about overutilization of imaging in medicine, as well as changes in the reimbursement landscape. Many insurance carriers began requiring precertification, limiting the clinical reasons for and requiring accreditation for outpatient facilities performing these procedures. This, combined with the drastic reductions in reimbursement rates, had many wondering about the future viability of SPECT imaging.

When the isotope shortage began, it was sporadic and unpredictable, but many were still able to receive technetium products on a regular enough basis to continue to schedule procedures somewhat normally. As it continued, many physicians and laboratories reported having to cancel procedures, refer patients to other diagnostic imaging modalities, such as stress echocardiography, or were forced to perform SPECT MPI with 201-thallium.

The suboptimal imaging characteristics of 201-thallium, however, make it unacceptable to use with obese patients and it increases the total radiation exposure per study by 25 to 30 percent. It also, not infrequently, produces a false positive study, which may result in other unnecessary procedures, such as cardiac catheterization. In some regions of the country, this had lead to suboptimal patient care and a decreased confidence by referrers in how to reliably diagnose and manage their patients with coronary artery disease (CAD).

For laboratories with access to positron emission tomography (PET) , the isotope shortage has not had as negative an impact. Facilities that were already performing cardiac PET MPI with rubidium-82 (Rb-82) or nitrogen–13 (N-13) ammonia, even on a limited basis, were able to shift many patients to PET. Others that had a PET scanner, but were not yet performing cardiac MPI, were able to purchase an Rb-82 generator in order to offer this procedure in lieu of SPECT. In both cases, labs were able to reduce the amount of cancellations, referrals to other imaging modalities and to unnecessary procedures.

A Blessing in Disguise?

Many believe the isotope shortage has been a blessing in disguise for cardiac PET. Although the capability existed and continued to undergo major advances in technology over the past several years, cardiac PET, for reasons including cost and space requirements, had not gained the same popularity or utilization as oncology PET. This was despite the demonstrated advantages of PET compared to SPECT.

Although SPECT MPI has been used for diagnosis and management of CAD for more than 30 years and is a reliable, cost-effective and well validated imaging technique, until recently it has seen little advancement in technology. SPECT also has several limitations, including long protocol times, it is prone to artifacts that may produce uninterruptible or false positive studies, it is not usually performed with attenuation correction, uses suboptimal tracers and may underestimate the extent of CAD.

When compared to SPECT MPI, PET imaging has demonstrated improvements in image quality and diagnostic accuracy. It produces less radiation exposure to patients and has faster acquisition protocols. PET tracers possess a higher (511 compared to 140 keV) imaging energy and are more linear to increases in myocardial blood flow when compared to the technetium agents, resulting in less attenuation artifacts. PET also has better spatial resolution and provides increased count statistics. PET is always performed with attenuation correction and the gains in image quality correlates into improved interpretive certainty.

There is also an advantage of diagnostic accuracy in PET over SPECT MPI.1,2 A recent meta-analysis by Nandular et al. demonstrated higher specificity and sensitivity of 95 percent for the diagnosis of CAD when compared to coronary angiography.1 Another study completed by Bateman et al. in 2004 compared SPECT MPI performed with 99mTc-sestamibi and PET with Rb-82.2 This study demonstrated that PET had a higher sensitivity, specificity and accuracy when detecting overall CAD and when detecting disease in individual coronary vessels. It also demonstrated that PET had a higher diagnostic accuracy when comparing gender, body mass index and multi-vessel disease.

Another major advantage of PET over SPECT is increased procedure efficiencies and patient throughput. A SPECT MPI, depending on type of stress performed, may take up to two and a half to four hours to complete. This time decreases the amount of procedures that may be performed on a daily basis and also may result in decreased patient satisfaction. With the current tracers being used to perform PET MPI, the overall acquisition time per study is about 30 minutes with a PET/CT scanner and 45 minutes with a dedicated PET system.

The only current disadvantage of PET compared to SPECT when using Rb-82 as the tracer is the inability to perform treadmill exercise. Due to the short (75-second) half-life, the only option is pharmacologic stress. This is not acceptable in all patients, as exercise tolerance and responses in blood pressure and heart rate are important diagnostic and prognostic indicators when determining course and type of treatments for CAD. Therefore, those patients who are capable of performing exercise stress may not be good candidates to shift from SPECT to PET as a diagnostic choice.

A Return to ‘Normal’

Most in the nuclear cardiology community are anticipating and/or are hoping for a return to the status quo as the production and supply of isotopes ramps back up to normal capacity. Given some of the major changes that have occurred over the past 15 months — including national healthcare reform, continued scrutiny and debate of overutilization of diagnostic procedures involving radiation exposure and increased utilization of cardiac PET MPI — it may be time to reconsider what a “normal” landscape in nuclear cardiology should or will look like moving forward.

Even with a supply of isotope closer to normal levels, it will take time for the field to rebound. Physicians will have to regain confidence in ordering a study without worrying that it will get canceled. Some will just continue to rely on the other modalities.

At the same time that efforts are being made to reposition SPECT as an available option, the Atomic Energy of Canada Limited (AECL) has scheduled another extended outage as part of the Chalk River Laboratories, National Research Universal (NRU) reactor’s return-to-service activities for some time in spring 2011. As part of NRU’s ongoing operations, the reactor will be operated on a 28-day cycle, which will include regularly scheduled five-day outages.

The extended outage in the spring will occur just in time for SPECT MPI to have regained some momentum. This, combined with the fact that the Chalk River Reactor may possibly be taken off line permanently some time in 2016, should prompt leaders in the field to evaluate options.

Even though there is considerable lobbying occurring to convince the U.S. government to create a domestic supply of medical isotopes, this may not be enough. In a political and societal environment that is demanding great healthcare in a much more cost-effective manner and doing so by performing diagnostic procedures with the least amount of radiation possible, it will almost be for us to redefine normal for the field of nuclear cardiology.

The good news is there are options to do this. The continued awareness and growth of cardiac PET MPI as a reliable procedure combined with continued efforts to improve and advance SPECT MPI technologies should give nuclear cardiology the new and improved normal that is needed to survive.

April Mann is currently the manager of noninvasive cardiology at Hartford Hospital in Hartford, Conn. She has been at Hartford Hospital for several years and her roles have included manager and supervisor of nuclear cardiology and staff technologist in nuclear cardiology and nuclear medicine. Mann received her associates degree in science for nuclear medicine technology at Springfield Technical Community College in Springfield, Mass., and her bachelor degree in arts for healthcare management at Elms College, Chicopee, Mass. Other accomplishments include several presentations and publications on a variety of nuclear cardiology and management topics.


1. K.R. Nandalur, et al. Academic Radiology 2008; 15 (4):444-51.

2. T. M. Bateman, et al. Journal of Nuclear Cardiology 2006; 13 (1):24-33.


Trends in Cardiac Nuclear Imaging

Technology in the field of nuclear cardiac imaging — single photon emission computed tomography (SPECT) and positron emission tomography (PET) — has been somewhat stagnant over the past decade. However, there are some recent advancements in both radiotracers and hardware that could change this field of imaging.

“This is a very exciting time in nuclear cardiology,” said Diwakar Jain, M.D., FACC, FRCP, FASNC, professor of medicine, director of nuclear cardiology, Drexel University College of Medicine.

He spoke to Diagnostic & Interventional Cardiology magazine to highlight several advancements in the field of cardiac nuclear imaging.

Improved SPECT Cameras
New gamma cameras entering the market are much faster and offer better quality images than previous versions. Three are currently on the market that use solid-state, cesium iodide detectors that directly convert gamma rays into electrical impulses, instead of traditional sodium iodide detectors that first convert the rays into photons that are then converted into electrical signals. This reduces a step in the image generation process and increases the quality of the image.

“These cameras are much better quality and have better resolution. They are somewhat new and expensive, but with time they will become more affordable,” Jain said.

Heart Failure SPECT Imaging
A new radiotracer, iodine 123, (AdreView) is being developed by GE Healthcare to image the sympathetic nervous system to help improve heart failure (HF) screenings. HF impairs uptake of this agent.
Jain said HF is usually graded based on ejection fractions, but there is a lot of overlap between the severity of the different New York Heart Association HF classes. He said the new agent may offer a more accurate stratification of HF.

The tracer is expected to have a big impact on determining which HF patients should receive an implantable cardioverter defibrillator (ICD) or cardiac resynchronization therapy (CRT) device. Jain said only about 10 percent of these are ever activated in HF patients, but are widely implanted as a precaution. He said the iodine 123 may help identify which patients will actually benefit from these devices.

Phase III clinical data have been submitted to the FDA and it is possible the tracer could receive FDA clearance by the end of 2010. If cleared, Jain said it would be the first new SPECT radiotracer cleared by the FDA since Myoview in 1994.

Results from the ADMIRE-HF (AdreView Myocardial Imaging for Risk Evaluation in Heart Failure) trial were published in the May 2010 issue of the Journal of the American College of Cardiology. The prospective study evaluated cardiac sympathetic nerve imaging using the AdreView. According to the results, in appropriately selected patients with heart failure, the imaging procedure can alert clinicians to the potential need to consider additional treatments.

Hybrid Imaging
Combined SPECT/computed tomography (CT) imaging systems are being used for better attenuation to create better images. The CT data also offer an anatomical roadmap to pinpoint specific anatomy and match it to the nuclear images.

Theses hybrid systems remain pricey, but have the advantage of being used as standard CT scanners when SPECT imaging is not being performed to increase room and device utilization.

Isotope Shortage Aids PET
PET Imaging offers better image quality and faster scanning times than SPECT, but Jain said it is not widely used in cardiac imaging. The main reason is PET is more expensive and the isotopes have such a fast decay rate they must be created onsite using a cyclotron, which greatly limits their availability.

Jain said one boost to PET in the past year is due to the SPECT isotope shortage caused by the shutdown of the Chalk River Reactor in Canada. He said the reactor is back online, but as with all the medical isotope reactors in operation around the world, it is old. All of these reactors will have periodic shutdowns for an increasing amount of maintenance.
PET can use four or five different radiotracers. The standard one used in cardiac imaging is rubidium 82 (CardioGen 82).

“The biggest issue with rubidium is the cost – it is very, very expensive, $30,000 to $40,000 per month,” Jain said. “Rubidium 82 only has one use — for cardiology, but it does not make sense with lower volume labs.”

The short 75-second half-life of the radiotracer is also a drawback. Jain said it forces use of pharmacologic stress rather than the preferred method of exercise stress.

Other isotopes can be used for cardiac imaging, including oxygen 15 and nitrogen 13, but they have not been commercialized and also require production in an on-site cyclotron because of a short 10-minute half-life, Jain said. Cyclotrons are usually only available at research facilities or at extremely high-volume labs that image 30-40 patients a day to make the massive hardware investment feasible.

“Radiotracers are the limiting factor with PET,” Jain explained.

Deficit Reduction Act Reverses Trend
A few years ago the trend in cardiac nuclear imaging was toward smaller, less-expensive cameras aimed at expanding office-based imaging. However, with the Centers for Medicare and Medicaid (CMS) instituting the Deficit Reduction Act (DRA) a couple of years ago, the brakes were put on office-based imaging. The act instituted a 30 percent cut in office-based imaging, because of the CMS perception that many of these self-referrals are motivated by revenue rather than patient diagnostics.

New PET Agents
Currently in trial is a new fluorine 18 (F18) PET tracer developed by Lantheus that has a two-hour half-life, allowing it to be produced at a commercial cyclotron and transported to numerous hospitals in the area. Lantheus presented phase II data at the 2010 Society of Nuclear Medicine (SNM) annual meeting for its flurpiridaz F18 injection. The data showed better image quality and an increase in defect size compared to SPECT.

“The results have been very promising,” Jain said. “It has all the benefits of PET imaging, which is inherently better than SPECT imaging.”
He said there is a reasonable chance the FDA may consider approval for the agent in 2011.

Another tracer that could potentially make cardiac PET imaging more accessible and widespread is gallium 68. Jain said it has the advantage of the parent isotope, germanium 68, having a 271-day half-life. This allows it to be shipped to imaging facilities in a generator and allows long-term use. Once activated, the gallium 68 isotope has a half-life of about 68 minutes.

“This would clearly be a big development,” Jain said.

Potential generator costs of between $12,000 to $20,000 a year would definitely be a price break advantage over a rubidium 82 generator costing between $30,000 to $40,000 per month.

Direct Ischemic Imaging
Another innovation being researched by Jain is myocardial ischemia imaging to directly identify damaged myocardium, rather than imaging for evidence of ischemia. He said ATP, usually in the form of free fatty acid, is generally used by healthy heart muscle in the presence of oxygen. However, when oxygen is not available, as in ischemic tissue, the muscle can convert glucose into energy. Jain said deoxiglucose (FDG) can be used as a biomarker to image these areas in combination with a different set of SPECT camera collimators.

He said research so far shows ischemic imaging seems to be less prone to imaging artifacts that are common in standard SPECT imaging.
“I view this as a very futuristic imaging concept,” Jain said.

“Reimbursement is not available in the U.S. for this until a large study proves it works and is safe.”