Source: The Oak Ridger | Carolyn Krause/Special | March 19, 2020
An important medical radioisotope used to diagnose and treat more Americans than residents of any other country is not made in America. It is produced in five aging foreign nuclear research reactors, several of which will shut down in the next few years.
“Visualizing the Medical Isotope Crisis,” an article in the January 2017 issue of Scientific American, stated, “As the few nuclear reactors that produce technetium-99 prepare to shut down due to age and risk of breakdowns, doctors are increasingly worried about shortages.”
Carmen Bigles and her team at CoquÍ Pharma aim to change this situation, partly in response to an act of Congress. The company’s plan is to construct by 2026 a large facility housing two 10-megawatt, open-pool nuclear reactors on Duct Island.
This 206-acre tract is part of the Oak Ridge Heritage Center, an industrial park just east of East Tennessee Technology Park and near the site for the proposed new Oak Ridge airport.
In a recent talk to Friends of Oak Ridge National Laboratory, Bigles, who is the founder, president, chair of the board of directors and CEO of CoquÍ Pharma, said the firm will produce molybdenum-99, which will be separated from low-enriched uranium (LEU) targets after they are irradiated in the two small reactors.
Moly-99, as it is often called, decays to technetium-99 (Tc-99m), the most widely used medical radioisotope. It is used in 80 percent of all nuclear medicine procedures using single-photon emission computed tomography, or SPECT.
“The United States is the largest global consumer of technetium-99 yet has no manufacturing capability,” Bigles said.
National interest in supporting a commercial medical isotope production facility in Oak Ridge, she added, is “driven by the need to ensure nonproliferation of weapons-grade uranium and to overcome the problems of impending supply shortages, capacity constraints and increasing prices.”
In 2012, Congress passed the American Medical Isotopes Act, which mandates that research reactors used for medical radioisotope production in the U.S. must operate on LEU, not weapons-grade, highly enriched uranium (HEU, which contains more than 20 percent uranium-235). The act calls for the U.S. Department of Energy secretary to evaluate and support projects for the production in the nation of significant quantities of molybdenum-99 (precursor of technetium-99) for medical uses.
Technetium-99m is used in 50,000 procedures each day in the United States. The medical isotope is employed mostly for myocardial perfusion imaging (56 percent) and bone scans (17 percent), but also can be used for imaging tumors, infection, and renal, thyroid, respiratory and other cardiovascular disorders.
It is also used in research looking for ways to develop drugs to treat Parkinson’s and Alzheimer’s diseases, as well as dementia, because technetium-99m reveals the brain’s functionality.
Myocardial perfusion imaging using SPECT is a non-invasive test that shows how well blood flows through, or perfuses, the heart muscle. It can reveal areas of the heart muscle that receive insufficient blood flow, as well as any impairment in the ability of the heart muscle to pump blood.
CoquÍ Pharma’s biggest challenge is financing to support construction of its new facility, Bigles said.
The company plan is to build two 10-megawatt nuclear research reactors. INVAP is an Argentinian nuclear engineering firm that CoquÍ Pharma has contracted as the technology designer of the facility for the Oak Ridge site.
“CoquÍ Pharma is the only U.S. company that has an exclusive license with INVAP, whose technology was previously used by an Australian company, the source of part of the U.S. medical isotope supply,” Bigles said. The small reactors would operate on LEU fuel and irradiate LEU target plates to produce Mo-99.
Bigles is hoping that the proposed Oak Ridge airport is built by the time the CoquÍ Pharma facility is operating because it will help the company get the needed medical isotopes in time to patients scattered across the nation. The process from irradiation until delivery of the medical isotope to the patient is 14 to 15 days. Here’s the reason why it’s important to have an airport only minutes away.
Two days after the LEU target is irradiated in a reactor, Mo-99 (a decay product of U-235) is separated, purified and placed in a generator for shipment to a patient. Mo-99 has a half-life of 66 hours. After 33 hours, half of it is gone.
One of its decay products is technetium-99m, which has a half-life of six hours. The generator in which this valuable medical isotope is produced must be transported to the patient in one to two days.
Some 1,500 construction workers will be needed to build the facility and install the two reactors and other equipment. When it begins operations in late 2026, CoquÍ Pharma will have 200 permanent high-tech employees who earn an average base salary of $85,000.
The Oak Ridge Y-12 Nuclear Security Complex, which has blended down HEU from weapons to make LEU, will supply LEU for targets and fuel assemblies (which will be made in Argentina) at CoquÍ Pharma’s medical isotope production facility (MIPF) on Duct Island.
The Oak Ridge MIPF will use twin open-pool reactors similar to the reactors in the INVAP-designed OPAL facility in Australia and most recently in Argentina. Open-pool reactor design is commercially proven and produces FDA-approved medical isotopes in Australia, Bigles said.
CoquÍ Pharma has to jump through several hoops before construction can start, Bigles explained. By 2021 it plans to submit an application for a license to the U.S. Nuclear Regulatory Commission (NRC). While the application is being reviewed, CoquÍ Pharma’s team from INVAP and Gresham Smith, an architectural, engineering and environmental firm in Nashville, will finalize the detailed engineering of the MIPF.
In 2023, after the license application has been reviewed by the NRC, CoquÍ Pharma hopes to receive approval for construction, which will take place from 2024 through the early quarters of 2026. By the end of that year, the company hopes to be able to generate revenue.
Bigles, a native of Puerto Rico, said that the company is named after “CoquÍ,” a small frog endemic to Puerto Rico “and the loudest amphibian there.
“Like the CoquÍ, we are small but very loud,” she said.
And the company team hopes to make a big splash commercially on Duct Island.