The Real Particle: These Cyclotrons Generate Imaging Tracers On-site to Boost Precision Medicine

Every morning, a charter jet takes off from Helsinki, Finland, bound for Örebro, Sweden. Its cargo: radiotracers. These radioactive compounds are essential for molecular imaging scans, which reveal metabolic processes inside cells. Radiologist and nuclear medicine physician Håkan Geijer and his colleagues at Örebro University Hospital depend on positron emission tomography (PET) scans to diagnose disease - like cancer - and, perhaps most critically, identify the best course of treatment. The hospital buys the necessary tracers from a commercial firm in Finland, so Geijer and his colleagues work with only the compounds that have a chance of surviving the 350-mile trip. Because the radioactive components used in medical imaging decay quickly, they must be created within hours - or in some cases minutes - of the patient's scan. By the time the plane from Helsinki lands, half of those components are already spent.

These constraints have limited the types of imaging that clinicians at Örebro can offer. And, of course, the deliveries from Helsinki are subject to the vagaries of weather. "Every winter, at some point, there's fog at the airport and the plane can't land," Geijer says. "We don't get any tracers that day, so we have to send all the patients home." Any delay can disrupt the patients' treatment schedules, which is both nerve-racking and potentially dangerous for someone with cancer.

But this past April, the hospital installed a brand-new GE Healthcare cyclotron, a 20-ton particle accelerator that will generate enough radioactive material every day for hundreds of tracer doses. With tracers made on-site, Örebro clinicians can scan patients using shorter-lived isotopes to evaluate body processes like blood flow and heart function. The new cyclotron will also guarantee a steady supply, ensuring that patients get the quick, accurate, personalized diagnoses they need.

Örebro is part of a growing movement toward the adoption of precision imaging around the world. In fact, the cyclotron in Örebro is the 500th that GE Healthcare has installed, and the latest of the more than 100 new cyclotrons the company has delivered since 2018, including the first facilities in Iraq, Iceland, Kenya, Afghanistan, and Bangladesh. In regions where cyclotrons are still scarce, patients must travel significant distances for the scans they need, so each installation has broadened access to a higher quality of care. The cyclotrons operate much like gas stations, which must be installed at specific distances so that cars can travel the distance between them in order to operate and refuel. It's the same with cyclotrons: Because of the half-life of the isotopes, hospitals need to be a certain distance from the cyclotrons in order to get functioning isotopes for patients.

To create the radioactive ingredient in tracers, a cyclotron (which is the size of a walk-in closet, encasing circular copper electromagnets as wide as semi-truck tires) generates massive electromagnetic fields that accelerate charged particles to nearly a fifth of the speed of light, or approximately 37,000 miles per second. Careening along a spiral path, the ions slam into atoms selected for their specific chemical properties. The collisions provoke nuclear reactions, producing radioactive isotopes that emit energy as they revert to a more stable form.

Technicians then bind the isotopes to nonradioactive chemicals, called carriers, that particular cells consume as part of their normal processes. For example, the most common carrier, glucose, tends to congregate in energy-hungry tissues such as tumors. In approximately one hour, technicians are able to produce a liquid tracer that can be injected into or swallowed by a patient prior to imaging. Along for the ride, the radioactive isotopes emit energy that PET machines detect and represent as points of light on a scan. Doctors look for unusually bright areas to diagnose cancer and other disease.

Because PET scans expose the behavior of individual cells, they provide a precise picture of what's going on in a patient's body. "With PET, we can tell much more exactly where a tumor is, and if it has metastasized, than we could before," Geijer says. PET can also show at a cellular level how well the treatment is working. "If the medication is not efficient, you should immediately change course," says Karin Granath, the general manager of cyclotrons at GE Healthcare. "With PET, we don't have to wait to see if the tumor shrinks, because by then it may already be too late."

Cyclotron-produced isotopes are also crucial in theranostics, a developing field that fuses therapy and diagnostics. In this approach, radiologists use these isotopes to run PET scans to find proteins on malignant cells that will bind with carrier molecules. If the carriers attach to those proteins, the tumor lights up on the resulting image. Then technicians attach cancer-killing isotopes to identical carrier molecules, which ferry the treatment to the same cells that glowed on the PET scan.

"You see exactly what you treat," says Erez Levy, GE Healthcare's general manager for molecular imaging.

With theranostics, oncologists can tailor treatment to an individual patient's tumor cells. Unlike in traditional chemotherapy or radiation, the radiopharmaceutical agent combines a radionuclide and a targeting molecule that binds to cancer cells. This allows it to irradiate and damage targeted cancer cells while limiting radiation to healthy tissues. Over the past two years, theranostics has become an increasingly popular therapy for prostate cancer, giving patients with advanced disease new hope.

In Örebro, clinicians look forward to expanding the types of top-of-the-line precision imaging they offer. "We try to help our patients by giving them an accurate diagnosis," Geijer says. "To do that, we need good tracers. Cyclotrons are a fundamental part of our patient care."