Taking Imaging Innovations from Lab to Market

April 28, 2013








Guiding Treatment: FDG PET imaging helps physicians decide whether bypass surgery or inserting a stent will benefit certain patients.
Top row: Blood flow (perfusion) images show areas of the heart that are receiving blood (red/orange/yellow) vs. areas with reduced or no blood flow (green/ blue/purple).
Bottom row: Viability images show areas of the heart that are functional (viable) but “hibernating” (red/orange/yellow) vs. areas with scar tissue (green/ blue/purple). The cardiologist compares blood flow and viability images to look for matches or mismatches in the colour scheme.
Patient 1: The blood flow and viability images do not match. This tells the doctor there is reduced blood flow (purple) to areas of the heart where there is viable heart tissue (red). Bypass surgery or stenting would likely benefit this patient. Patient 2: The blood flow and viability colours match closely. This tells the doctor there is reduced blood flow as well as scar tissue in the same areas of the heart and bypass or stenting is unlikely to help.

Modern medical imaging allows doctors to see deep within the body in exquisite detail. Using small amounts of radioactive material called tracers, cardiologists can see in real time how well a patient’s heart is functioning.

The positron emission tomography (PET) imaging group at the University of Ottawa Heart Institute has the capacity to develop experimental tracers, conduct research and perform clinical imaging tests. Now, with one tracer, the group has brought the process full circle from early research, through clinical and regulatory approval, all the way to commercial production. And the imaging group has done it all on its own.

A heart attack can damage heart tissue and cause scarring. By giving a patient who has had a previous heart attack an injection of the PET tracer fluorodeoxyglucose (FDG), doctors can tell poorly functioning heart tissue that is still alive and could benefit from bypass surgery or stents from scar tissue that is unlikely to recover. Known as a viability test, this is an important tool to help guide care for certain patients.

FDG consists of a sugar molecule bound to a radioactive compound. “Heart muscle tissue that’s alive and healthy requires sugar for metabolism,” explained Linda Garrard, Research Manager for the Heart Institute’s Cardiac PET imaging research team. “In active, healthy heart muscle, there’s an uptake of FDG. If you’re not getting uptake in a particular area, then that tissue is mostly scar, and we know that bypassing that artery won’t gain the patient any benefit. You would just be sending blood to a part of the heart that’s not working.”

In the late 1990s, the PET imaging team received a grant to start building a cardiac PET centre that included a cyclotron to produce radiotracers such as FDG. With that jump-start, the Heart Institute quickly assumed a major role in radiochemistry research in Canada.

In 2003, the team began the PARR-2 clinical trial, which would show that using FDG PET to guide treatment of coronary artery disease could benefit certain high-risk patients.

The results of this research and the Heart Institute–led Ontario Cardiac FDG PET Registry (CADRE) helped change health policy in Ontario by providing the scientific basis for the provincial insurer to approve coverage of FDG PET viability testing. “We had a celebration when FDG was finally approved as an insured service,” said Garrard. “We’d been working on it for 12 years, and to see how the research we did eventually changed policy—not many people are fortunate enough to see that kind of process happen all the way through.”

The Heart Institute is also now responsible for the coordination of the Provincial Cardiac FDG Special Access Program, which is expanding the use of FDG for other, non-insured indications. The PET imaging group is currently assessing the clinical use of FDG PET for diagnosing inflammation in the aorta and for cardiac sarcoidosis—a buildup of abnormal cells in the heart that can lead to arrhythmias and heart damage. Through this special access program and a provincially-sponsored clinical trial, FDG imaging for sarcoidosis is expected to become an insured service within the next two to three years.

The decision to move into manufacturing was not an expected one for a medical facility, but Dr. Rob Beanlands, Chief of Cardiology and founder of the Heart Institute’s PET program, explained that it made sense from several perspectives: “First of all, it’s good for patient care. The manufacturing approval process is like an accreditation process. You’re validating that everything meets a certain standard. Secondly, it shows that we have the ability to take a tracer from experimentation all the way to clinical care. That’s the ultimate in translation, and it has attracted potential academic and industry partners interested in collaboration.”

Because Health Canada classifies radiotracers as drugs, any institution wanting to produce one for sale requires certification as a drug manufacturer. Without any help from industry partners, the cardiac PET imaging group prepared a new drug submission to commercially produce FDG. The group received notice of compliance in December 2010 for the production of FluorOHmet (Fluor for fluorodeoxyglucose, OH for Ottawa Heart and met for metabolism imaging) and is now finishing the application for an establishment license. In all, it’s been a lengthy and exacting undertaking.

“We have the ability to take a tracer from experimentation all the way to clinical care. That’s the ultimate in translation.”

 

– Dr. Rob Beanlands, Chief of Cardiology, UOHI

 

“For an academic institution to do this on its own is a huge process,” said Garrard. Once officially certified, the production team, led by radiochemist Jean DaSilva, will be able to commercially produce and sell FDG to area hospitals, providing a small revenue stream to support the radiochemistry laboratory, personnel and equipment. The Heart Institute currently provides a local, reliable source of FDG for cardiac imaging at the Heart Institute and oncology at The Ottawa Hospital. FDG has a half-life of just under two hours, meaning that the radioactive energy of the tracer reduces by half every hour. With shipping suitable only within a two-hour radius, production of FDG is by necessity a local affair.

“There will always be products that we make for research purposes,” added Dr. Beanlands. “That’s part of who we are. But other tracers we make in-house with industry partners will likely become commercial products. This all bodes well for us. It provides us with additional resources to run the facility and to continue doing research.”

One project that has recently grown from idea to commercialization, with industry partner DraxImage, is a portable rubidium generator for cardiac perfusion imaging. This diagnostic test is used to see how well oxygen-rich blood reaches various parts of the heart. Rubidium is a radioisotope with an extremely short half-life—less than 90 seconds. “There’s not even time to draw it up into a needle, walk to the patient and inject it. It would mostly be gone by then,” explained Garrard.

The rubidium produced by the rechargeable generator, designed at the Heart Institute by physicist Robert deKemp, can be infused directly into a patient lying in a PET scanner with the use of a pump system, which was developed by engineer Ran Klein, Manager of the Cardiac Imaging Core Lab. The device has the potential to make rubidium and the test more widely available. In the ongoing Rubidium-ARMI clinical trial, Heart Institute investigators are testing not only the accuracy of rubidium-based imaging compared to a more common, cyclotron-produced radioisotope but showing that institutions can easily adopt the technology.

Following initial training, participating centres have found the generators to be user friendly. The cardiac PET team hopes that its research initiatives and investment in commercial activities will help to support continued innovation. “Our goal is to keep doing what we can to improve diagnosis,” Garrard concluded.