ORNL Radioisotope Research and Development Section head Sandra Davern. Image credit: Carlos Jones, ORNL
When people a decade from now face a cancer diagnosis, they may well turn to East Tennessee for help.
The region is well-positioned to become a focus for nuclear medicine, or radiopharmaceuticals, which use radioactive isotopes to diagnose and treat cancer and other diseases. East Tennessee boasts two major research institutions in this field — ORNL and the University of Tennessee.
While radioisotopes have been used in medicine for decades — ORNL first shipped a medical isotope, carbon-14, to a St. Louis hospital in 1946 — the field is in its early stages in some respects.
“We are at the beginning of what will be a wave of radiopharmaceutical implementation for cancer,” said Sandra Davern, head of ORNL’s Radioisotope Research and Development Section. “So radiopharmaceuticals are really only starting to be used to treat cancer.”
State leaders would like to see the region become a national center for developing new and better treatments and conducting the clinical trials needed to bring these advances to patients. For that to happen, though, much work lies ahead, including, critically, the development of a robust workforce of physicians, physicists, radiopharmacists and technicians.
The benefits of nuclear medicine
Medical isotopes serve at least two purposes. The first is diagnostic: An isotope is attached to a molecule that seeks cancer or other disease for visualization. The radiation emitted by that radioisotope allows the disease to be pinpointed by technology such as a PET-CT scan. (PET scan technology was developed by an Oak Ridge company, EG&G ORTEC, in the 1970s and commercialized in the 1980s by spin-off CTI Molecular Imaging, which was based in Knoxville and is now owned by Siemens.)
The second purpose is therapeutic: In this case, instead of just observing cancer cells, the isotopes’ job is to seek and destroy them.
Currently, radioisotopes are used much more widely to diagnose disease than to treat it, simply because that technology is farther along.
“The nuclear medicine world in East Tennessee is small but growing,” Davern said. “We have a lot related to imaging disease and making diagnoses.”
Dustin Osborne, director of the Molecular Imaging and Translational Research Program within UT’s Graduate School of Medicine, agreed.
“We’ve seen massive growth in our PET-CT usage in the hospital, and regionally you find that same sort of growth.”
On the therapeutic side, Osborne said, UT Medical Center uses two approved radiopharmaceuticals, both with the radioisotope lutetium-177. One, called Pluvicto, treats prostate cancer. The other, called Lutathera, treats neuroendocrine tumors such as those found in the pancreas.
“We’re treating prostate and neuroendocrine tumor patients here,” he said, “but you’re also seeing this growth now from Vanderbilt [Vanderbilt University Medical Center in Middle Tennessee] to a group in the Tri-Cities area [in the northeastern corner of the state] that are delivering this therapy. So it’s growing in the state and growing in this area.”
So far, he said, these therapies can be both more effective than chemotherapy and have less severe side effects. He pointed to the neuroendocrine therapy Lutathera as an example.
“Nearly 80 percent of the patients in clinical trials saw a 30 percent decreased size of the disease in their body,” he said, “which is a massive difference. In chemotherapy, if we get 20 percent efficacy on something, that’s good.
“And the side effects for chemo are far, far worse than what we see with radionuclide therapy, where so far the only patient complaints have been fatigue two or three days after the procedure, and sometimes a little bit of nausea.”
Benefits to the community
A growing nuclear medicine industry in Tennessee will not only benefit the economy, it will also be a boon to people in the region who need treatment and access to clinical trials.
Davern noted that cancer rates are relatively high in the Southeast and Appalachia, especially among low-income residents. Generally, these are also people who lack the means to travel across the country for treatment.
“If you do an analysis of death rates from cancer, and you compare that to income for these people, you see that over the whole of the U.S., it is often the poorest people who have the highest cancer death rates.
“And so if we can have the infrastructure to support this imaging and this therapy in Tennessee, we can benefit these communities who likely don't get to travel.”
ORNL research
Davern and Osborne agree that many more promising therapies are on the horizon. To get there, though, researchers have some technical challenges to solve.
One is to develop more and more effective cages — called chelators — for attaching radioisotopes to the locator molecules. To that end, Davern heads a Laboratory Directed Research and Development initiative at ORNL called Accelerating Radiotherapeutics through Advanced Molecular Constructs, or ARM.
“With the technology that's out there,” she said, “you need to heat the reactions pretty intensely to be able to get the radionuclide to go into that cage, and that would destroy any kind of biological molecule like an antibody. So we're looking at ways to do this in more physiologically relevant conditions so that you don't destroy these more sensitive targeting molecules.”
The project is also looking closely at other promising isotopes, including actinium-225. ORNL is currently the principal supplier of this isotope for medical research. Other medical radioisotopes produced at the lab using the High Flux Isotope Reactor include actinium-227, which is the critical raw material for the radium-223 that goes into Bayer’s prostate cancer drug Xofigo.
“Actinium-225 is what we think will be next in line for regulatory approvals,” Davern said, “due to how they're moving through clinical trials. Right now we produce most of the actinium-225 available for these clinical trials.”
Nuclear medicine needs workers
Davern is also an anchor researcher for a workforce-focused initiative from the University of Tennessee-Oak Ridge Innovation Institute.
“What we're trying to do with the convergent research initiative is to help build across the whole state — from Memphis to Knoxville and Oak Ridge — a capability that builds up both the education and the workforce to be engaged in developing that next important radiopharmaceutical,” she said.
“So we can do the R&D, but we're also thinking about that next generation of worker and researcher who will be necessary to attract new industry to the state.”
Davern noted that the workforce needs of the nuclear medicine industry mesh with those of the nuclear power industry, especially for people who work directly with radioactive isotopes.
“We have similar workforce and education needs as people in the nuclear energy industry to work on the radioisotope production side, both in nuclear engineering and in the technician side for working with radioactive materials and the support side for keeping track of nuclear materials,” she said.
Many more workers will also be needed in hospitals, Osborne said.
“Not only do we have a shortage of technologists to run the machines and shortages of physicists like me to do the dosimetry calculations and set up the scan protocols, we have shortages also of radiopharmacists, who are the ones who can release the drugs for us to use in the first place.”
The future of nuclear medicine in East Tennessee
If the field delivers on the promise it is showing, those needs will only multiply. Davern believes East Tennessee can take advantage of the coming boom in nuclear medicine, but it will take hard work.
“We have all the pieces and parts to be an ecosystem for this development,” she said, “but it's how to make them all connect. The whole Tennessee corridor has really interesting capabilities, because we can have medicine linking with research linking with the national lab and going from biology all the way through to radioisotope production.”
Osborne noted that the more these therapies succeed, the more people will insist on having access to them.
“The fact that these are so effective with less side effects than our current standards of care — what a great combination, if we can be more effective and less impactful on the patient’s quality of life.
“To say that I’m excited about where we’re going is still a massive understatement.”
