The University of Ottawa Heart Institute in Canada was one of a handful of facilities that started using thallium-201 after the 2009 shutdown of the Canadian Chalk River nuclear reactor in Ontario led to a shortage of technetium-99m. Technetium is the primary radiotracer used in SPECT heart scans, but the supply chain for the radioisotope is fragile and complex leaving many facilities — like the Ottawa Heart Institute — with limited options. Unfortunately, thallium didn't live up to technetium when researchers at the facility recently analyzed data from patients after the switch from technetium to thallium: Thallium increased downstream testing, costs, and radiation exposure when compared to technetium.

With roughly 50,000 technetium SPECT exams performed in the U.S. each day, it's a sure bet that a solution is in the works to deal with the supply chain issues around technetium. According to experts, that solution is likely to come with new radiopharmaceuticals that will shift myocardial perfusion imaging away from SPECT and toward PET.

"Nuclear cardiology is ripe for a major change," Dr. Samuel Wann, a cardiologist at Columbia St. Mary's in Milwaukee, Wisc., told DOTmed News.

One promising candidate is N-13 ammonia, which has been around for decades but could soon be available on a larger scale for PET heart scans.

Ammonia has one big caveat: Unless a facility is a stone's throw away from a cyclotron, the isotope cannot be used for PET imaging studies due to its short half life of only 10 minutes. That's why up until this point, ammonia has mainly been confined to academia where researchers have access to large cyclotrons. Ionetix, a company based in San Francisco, introduced an N-13 ammonia PET production system at the Society of Nuclear Medicine and Molecular Imaging conference in early June that includes a mini cyclotron for ammonia production. This means facilities can produce the isotope right on site for use with PET scanning.

"It's a super conducting cyclotron and able to maintain the production capabilities, but in a footprint that is literally a fraction of what a traditional cyclotron is," David Eve, vice president of sales and business development for Ionetix, told DOTmed News.

Eve hopes this could turn out to be a big growth area for cardiac PET since providers will be able to easily adopt the technology.

In addition, the need for improved detection of cardiovascular disease cannot be ignored. According to the American Heart Association, heart disease is the leading cause of death for both men and women in the U.S., causing roughly 730,000 deaths each year.

Ammonia has a competitor, however. Part of the success of Ionetix's PET radiopharmaceutical systems depends on a novel PET tracer from Lantheus Medical Imaging called flurpiridaz F 18. Phase 2 trials for flurpiridaz showed that it improved image quality over SPECT studies. It also has the ability to reduce the loss of image accuracy. Flurpiridaz recently received clearance to enter its second Phase 3 trial.

Both ammonia and flurpiridaz are known for producing high quality images with quantitative regional flow (most PET/CT scanners come with quantification technology built in), meaning the images are easier to read and the data is cleaner. According to Wann, ammonia produces good images because it's a high-powered agent when it travels through the body. It can also travel through obese patients much more efficiently because it's opaque. In addition, its high energy level means less radiation is given to the patient.

Many cardiology practices have already chosen PET over SPECT with rubidium-82 as one of the few radiotracers available to perform these studies. Rubidium is used in over 90 percent of cardiac PET scanning. It's produced in a generator and available from one company only-- Bracco Diagnostics. But rubidium has a half life of only 75 seconds. Its supply is also unstable and most recently, there have even been safety concerns around it.

"In the past three years and for the foreseeable future Bracco will continue to suffer from supply shortage issues. Conceivably both ammonia-13N and flupiridaz-18F might relieve some portion of the supply issues experienced by Bracco's Cardiogen-82 generator," Wayne Webster, a consultant with Proactics, told DOTmed News (Disclosure: Webster sits on the editorial advisory board of DOTmed).

While studies have shown that PET imaging with rubidium can do a better job of detecting coronary heart disease than technetium, Wann said he doesn't think rubidium is a real player in "the game changing machine" where new tracers, like ammonia and flurpiridaz, enter the picture. Supply problems and inferior imaging results compared with ammonia and flurpiridaz give it less of an edge, according to Wann.

To date, approximately 900 subjects have been imaged with flurpiridaz with more studies on the way when the Phase III trial begins.

"We are unable to understand its [flurpiridaz] full impact because the radiopharmaceutical has not been used routinely in multiple thousands of cases. This is usually when we begin to truly understand how things work when the radiopharmaceutical is used by many and not under such tight controls as there are in clinical trials," said Webster.

However, a few papers and some anecdotal evidence points toward improved image resolution for flurpiridaz over technetium.

"I'm not aware of any controlled comparison with other PET radiopharmaceuticals," said Webster.

The jury is still out on whether Ionetix's ammonia system and flurpiridaz can live up to expectations -- and how the costs will compete.

Flurpiridaz has a 109 minute half-life, which means it can be produced at nuclear pharmacies and distributed to cardiac PET user on demand. Some might prefer this over the commitments-- but financial and otherwise -- that come with investing in a cyclotron, whether it's miniature or not.