Y-12 Historian, Ray Smith

Although Oak Ridge, Tennessee, began as a “secret city” during World War II, the nuclear science that ultimately ended the war also led to innovative advancements in medicine that continue today. From cardiovascular imagining and PET scans, to treatments for cancer and other diseases, many medical procedures utilize stable isotopes or radioactive, radioisotopes, which were first separated and made radioactive in Oak Ridge.

“I am not sure that there’s ample understanding and appreciation for all of the technological advances that resulted from the Manhattan Project,” explained Y-12 Historian Ray Smith.

After the war ended, Dr. Chris Keim began the work of separating elements using the electromagnetic separating calutrons and producing stable isotopes for medical uses. According to Smith, calutrons that were no longer needed to separate uranium for the war effort were also used to separates isotopes of other elements, and this led to advancements in agriculture, biology, and medicine. Isotopes from various elements were separated in Building 9731 at Y-12 and sent over to the Graphite Reactor where they were made radioactive to become radioisotopes.

“That’s where the genesis of the nuclear medicine came from with those isotopes that were being created at the Oak Ridge National Laboratory in the late 40s and were being distributed to the hospitals around the country,” said Smith. “And, that program started as a result of the collaboration between the calutrons at Y-12 and the Graphite Reactor at what became the Oak Ridge National Laboratory [ORNL].”

During peacetime efforts, this second phase of science marked the first worldwide discovery of the medical isotope. The first shipment of radioisotopes from Oak Ridge was delivered to the Barnard Free Skin and Cancer Hospital in St. Louis, Missouri, in 1946.

Even though there are other ways to produce isotopes today, some can still only be separated with calutrons. However, the United States currently relies on foreign suppliers for these.

“What happened with the calutrons is that Russia undercut the price [of isotopes] in 1998 to the point that they ran the United States out of the business, and anyone who wants these isotopes now, worldwide, buys them from Russia,” said Smith.

The beta calutrons at Oak Ridge have been on standby since 1998. They remain the United States’ only source of separation for many of the isotopes; however, the location of the Oak Ridge calutrons at Y-12 also requires additional expense particulars and other security considerations.

According to Saed Mirzadeh, PhD, of the senior research and development staff for the nuclear medicine program fuel cycle and isotopes division at ORNL, national security issues affect the way that calutrons are handled. Because they can still be used for the enrichment of uranium, as they were initially during the war effort, the government does not want these machines to be misused.

“Due to some security issues, this adds extra expense…, and there is no way that they can pick it up and move it elsewhere,” said Mirzadeh.

Interestingly, a separation science is currently in the research and development stage at Oak Ridge for medical and industrial isotopes that will possibly supersede the calutron.

“Right now, the DOE [Department of Energy] and Office of Nuclear Physics is sponsoring some research in a smaller scale to come up with a replacement for the calutron…and this new machine will be smaller and combine both magnetic and centrifugation separations,” explained Mirzadeh.

Many radioisotopes developed from nuclear science exist for medical purposes.  For example, ORNL is the major supplier of actinium-225 worldwide.

“Actinium-225 is used for the treatment of leukemia, and right now, it’s on clinical trial at Sloan-Kettering Cancer Center,” said Mirzadeh. “That’s produced from a base material actually held here at ORNL. It was a defense related material, but we were able to extract some of the byproduct of it, and that is being used in medicine right now.”

Nickel was another one of the elements originally separated in the calutrons. Today, the Nickel-63 radioisotope, which is also produced at ORNL High Flux Isotope Reactor (HFIR), is used in batteries for pacemakers because of its long-lasting properties. 

“There are a number of medical isotopes produced in the U.S., but if it’s financially viable, we cannot as a federal government compete with them [private companies] because of the antitrust law,” added Mirzadeh.

Currently, the medical radioisotopes produced at ORNL are primarily for clinical trials at various cancer centers and universities.

“These are all under clinical trials, so the patient has to go through their doctors, and they make a determination from that end…. We are part of the federal government, and we cannot compete with the private industry,” said Mirzadeh. “Our job here is to take an isotope and bring it the market to the point that private industry becomes interested in it and carries it further to the completion.”

According to Mirzadeh, 90 percent of nuclear medicine revolves around diagnostic use through scanning procedures that incorporate a number of radioisotopes in various radiopharmaceuticals. However, his work in nuclear medicine focuses on the other 10 percent in therapeutic research using the radioisotopes that emit alpha particles to cure cancer.

Many of the radioisotopes used in the science of nuclear medicine are classified as radiopharmaceuticals, and these actually incorporate radioactive tracers.

“My current interest is taking the antibody that is designed to target a specific tissue or organ of the body and putting the radioactive isotope on it and injecting it into the bloodstream and letting the antibody take the isotope to where it has to go,” explained Mirzadeh. “It’s very much like a torpedo that has a load, and the torpedo detects where it has to go. When it gets there, you have the radioisotope that does the targeted radioimmunotherapy or provides a gamma ray that you can image it.”

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