Clinicians have a wide variety of scanners to diagnose what ails us. X-rays and CTs use ionizing radiation to visualize structures in the body. Ultrasounds and MRIs use sound waves and radio waves, respectively. But PET scans fill a different role.
Short for positron emission tomography, PET tracks tiny amounts of radioactively labeled molecules to determine where they go in the body. The technology is less focused on the structure of the body than on metabolism and function. While CT, MRI and the other imaging techniques may depict the anatomy, PET can tell us what cells in the body are actually doing.
This can be extremely useful. For example, because cells in tumors divide faster than normal tissue and are therefore “hungrier,” they tend to concentrate a radioactive sugar such as glucose. PET scans can see tumors as glowing bright spots.
The technology has other advantages, too. PET is being used as a tool to aid in the development of new drugs by determining if the drug goes where it is supposed to go or goes elsewhere in the body where it could cause toxic side effects. Finding that information early, before spending millions of dollars on clinical trials, could help streamline the drug discovery process.
And while PET has been around for decades, it still has shortcomings that keep it from fulfilling its potential. But perhaps not for long. Simon Cherry, distinguished professor in the Department of Biomedical Engineering, in collaboration with Ramsey Badawi, director of research in the Division of Nuclear Medicine, is working with colleagues at UC Davis and beyond to build a better PET scanner. Improved PET technology could provide faster, clearer scans, using less radiation.
The full-body PET scanner
One of PET’s main disadvantages is its narrow field of view. PET machines can only see the body in 20-centimeter chunks, which amounts to about 8 inches. To image the entire body, clinicians have to “step” it through one chunk at a time. Cherry believes the process could be improved.
“If we can develop a scanner that covers the entire body, allowing us to see the radioactively labeled molecules we have given the patient in all organs simultaneously, we can either drop the radiation dose by a factor of 40 or image 40 times faster,” says Cherry. “Rather than a scan taking 20 minutes, it could take just 30 seconds.”
The reduced radiation could benefit pediatric and other patients who might be vulnerable to radiation. It could be particularly helpful for patients who require several scans to track cancer progression or determine if a treatment is working. In addition, capturing scans much more quickly could mean images will be less blurred by movement of the patient, allowing physicians to get a clearer view of smaller tumors.
“If you ask someone to lie still for 20 minutes, they’ll do their best, but they move,” says Cherry. “Twenty or 30 seconds is more doable. Someone could even hold their breath for that long to eliminate motion caused by breathing.”
Cherry has been collaborating with Badawi on the EXPLORER program to build a two-meter PET scanner. The group is part of an international effort to make dramatic improvements to PET. Cherry and Badawi recently received a $15.5 million Transformative Research Award from the National Cancer Institute and other federal programs to complete construction of what will be the world’s first whole-body PET scanner.
The fruits of international collaboration
The advantages of a bigger PET scanner are so obvious, many people wonder why it hasn’t happened yet. The simple answer is the technological challenges are quite daunting. For example, a larger scanner means handling huge amounts of data.
To overcome this and other issues that prevent PET scanning from reaching its full potential, Cherry’s team is collaborating with researchers and companies around the world. The EXPLORER program, for example, also involves scientists at the University of Pennsylvania and the Lawrence Berkeley National Laboratory, as well as consultants from the United Kingdom.
Other collaborations focus on developments further into the future. In another ongoing partnership, the group is working with the Shenzhen Institutes of Advanced Technology (SIAT) in China to develop better data-handling technology.
“SIAT is a young institute,” says Cherry. “They have a lot of interest in PET technology but not much expertise. On the other hand, they have tremendous expertise in electronics, where we could use some help. It makes for a great partnership.”
The researchers also are working with scientists in Australia to perfect tracking technology that would provide clearer images when subjects are moving. They are also collaborating with Imanova, a London-based company that wants to use full-body PET to test new pharmaceuticals.
Perhaps the most interesting collaboration is with the research institute Fondazione Bruno Kessler in Italy and an Irish company called Sensl to develop a solid-state, low-light sensor. PET scanners, while advanced, still contain a relic from the 1950s – a vacuum tube, known as a photomultiplier tube. The scanner detects gamma rays from the radioactive tracer and converts them into visible light, which is then converted into electrical signals by the photomultiplier tube.
Cherry and collaborators are searching for a solid-state alternative, which would be more efficient and easier to manufacture, and could potentially improve image quality as well as reduce cost.
Fast scanning and reduced radiation are only some of the benefits full-body PET scanners could bring to patients. These devices could better track how far metastatic cancer has spread, monitor how patients are responding to treatment, or clarify how immunotherapy activates the body’s ability to attack cancer.
“This scanner could help with anything that’s a whole-body phenomenon,” says Cherry. “Think metastatic cancer, inflammation, immunotherapy – they’re all systemic and all relevant to cancer.”
Those are long-term goals, but in the shorter term, the technology offers another way to benefit patients: accelerated drug discovery.
A full-body PET scanner could follow a drug’s path through the body, helping pharmaceutical and biotech companies determine if an agent is hitting its target and whether it’s sequestered in the heart, liver or kidneys – a potential warning sign for toxicity.
The information could give medicinal chemists and pharmacologists early opportunities to redesign a molecule – or try another compound entirely – to avoid toxicity and move potentially life-saving drugs down the pipeline.
This possibility is already intriguing drug companies interested in the early prototype being developed by Cherry’s team. And though direct patient care is the ultimate goal, research applications could provide great benefits in the near future.
“We’re not positioning this as something that’s going into hospitals anytime soon,” says Cherry. “It’s really a tool to conduct these unique research and pharmacological studies. If we have this kind of performance, it could really change the kind of research we can do with PET.”