MO-99

Technetium-99m (Tc-99m) is used as a radioactive tracer in about two-thirds of worldwide diagnostic nuclear isotope procedures. Tc-99m is especially useful for nuclear medicine procedures because it can be chemically incorporated into small molecule ligands and proteins that concentrate in specific organs or tissues when injected into the body. This short-lived isotope (6-hour half-life) is “generated” as a decay product of its precursor molybdenum-99 (Mo-99) which has a mere 66-hour half-life (~1% decay per hour). Thus, Tc-99m and Mo-99 cannot be stockpiled and the Mo-99 must be made weekly or more frequently to ensure daily availability of Tc-99m.

The United States consumes about half of world production of Mo-99, yet, remarkably, no Mo-99 is currently produced domestically in the U.S.. The majority of U.S. supplies are produced in the National Research Universal (NRU) reactor at Chalk River, Ontario, and in the High Flux Reactor (HFR) at Petten in the Netherlands. The aging Chalk River and Petten isotope production reactors are both over 40 years old and are scheduled to be decommissioned, the first in 2016 and the other a few years later. (Europe’s other reactors, HFR, BR2, and Osiris, were commissioned in the 1960s and will also be reaching the ends of their planned lives between about 2015 and 2020.) While there are planned replacements for the Petten and other European reactors, security of supply of Mo-99 in North America is in serious jeopardy since the planned Canadian Maple reactors that were to replace the Chalk River reactor have been abandoned.

Millions of patients benefit from Tc-99m imaging procedures in the U.S. every year and the coming Mo-99/Tc-99m crisis is typified by an earlier unplanned Chalk River reactor shutdown that resulted in emergency parliamentary action to restart the reactor in response to the medical community outcry throughout North American over Tc-99m shortages. The crisis is also foreshadowed by the current lawsuit filed by MDS Nordion against Canada’s AECL for interference with economic relations and the anticipatory 2016 breach of the Mo-99 supply agreement that was to provide for continued Mo-99 supply through 2022.

Predominant Mo-99 production techniques suffer from staggering levels of inefficiency. For example, the Chalk River reactor relies on highly-enriched uranium (HEU) target fuel, of which only one unit of target fuel can be produced from over 200 units of natural uranium. Only about 3% of the HEU in the target is even fissioned during the six days that the HEU target is in the reactor. And of the 3% of HEU fissioned, only 6% of those fissions result in the formation of a fission product of mass number 99, which will decay into Mo-99. Most of that Mo-99 will decay and be lost in the several days it takes to prepare a Tc-99m generator and deliver it to a medical facility. Thus, much rare uranium is wasted in making the HEU target, most of the HEU in the target is wasted after producing only a small percentage of available fission products, most of those fission products are not of mass number 99, and most of the Mo-99 decays before it ever makes it to a patient who needs the fleeting Tc-99m.

There is a better way to produce Mo-99/Tc-99m that eliminates the major inefficiencies of current and proposed batch solid target processes. A liquid-fluoride reactor can produce a stream of Mo-99 continuously from inexpensive thorium, rather than in tiny amounts from expensive batches of largely wasted HEU targets, offering significantly greater efficiencies. Most of the advantages of LFTR technology derive from use of a liquid fuel instead of solid fuel and from use of molten salts coolant instead of water coolant.

Fission of uranium-233 (U-233) in the LFTR liquid core produces heat useful for electricity generation while continuously regenerating uranium-233 from a liquid feed of natural thorium. The fission of U-233 also produces Mo-99, much like the fission of HEU in solid target reactors, except that the liquid fuel of a LFTR captures Mo-99 as a tetrafluoride (MoF4), which can be fluorinated and continuously extracted online without shutting down the LFTR or interrupting the power generation process of the reactor. Thus, unlike costly radio-isotope production with dedicated reactors such as at Chalk River or Petten, Mo-99 production with a LFTR is simply a byproduct of operating the LFTR as a power reactor, affording significant cost savings.

Flibe Energy is actively developing LFTR technology for future electrical power generation, with demonstration and deployment anticipated 2015-2017. Once the demonstration LFTR is operational, additions of a chemical fluorinator unit and extraction operating procedures are necessary to produce Mo-99.

Flibe Energy recognizes the societal and market values of this life-saving product stream and is seeking partnerships with qualified pharmaceutical organizations interested in securing future distribution rights to Mo-99 we will generate. We welcome serious inquiries about strategic pharmaceutical partnerships for Mo-99 generation and distribution.


Competitive Comparison

Molybdenum-99 is currently produced by inserting small samples (“targets”) of highly-enriched uranium (HEU) into special research reactors at a handful of locations around the world. These research reactors differ from power-generating reactors in that they are designed to allow samples to be inserted and removed while under operation, thus they must operate at low pressure and are unable to generate electrical power. Large power-generating reactors also make sizeable quantities of Mo-99 but because they must operate under high pressure that Mo-99 cannot be removed in a timely manner before it decays away.

Within any reactor, regardless of its coolant or configuration, uranium-235 undergoes fission and about 6% of these fissions lead to the formation of a molybdenum-99 nucleus. The amount of Mo-99 begins to build up in the HEU target but it also begins to decay away. The target is typically left in the reactor until the rate of formation of Mo-99 (from fission) is balanced with the rate of loss of Mo-99 (from decay). This implies that much of the Mo-99 is lost before it is even removed from the reactor.

After the target is removed, it is cooled and chemically processed to remove the molybdenum (of which Mo-99 is one of several isotopes present). The molybdenum is shipped from the processing site to the location where it will be formed into “generators”, which are small, thermos-sized portable containers that hold molybdenum for medical use. Each of these steps consume precious time and each hour that transpires results in a 1% loss in the inventory of Mo-99. It is indicative of the great value of Mo-99 that a fuel as valuable as HEU can be consumed at such poor efficiency and yet still produce a valuable product.

Producing Mo-99 in a LFTR is an entirely different proposition. There are tremendous advantages over the current technique. First of all, the reactor is unpressurized, meaning that it can continue to produce electrical power while making other products. Secondly, the fuel is in a fluid form, facilitating the online extraction of molybdenum. Thirdly, molybdenum in fluoride media is very easily extracted using a technique that has already been identified.

For a small research and test reactor, the anticipated revenues from Mo-99 are substantially greater than might be derived from electricity sales, to such a degree that the Mo-99 production mission will likely supersede any desire to produce electricity.

Reports and Journal Articles:

Medical Isotope Production Without Highly Enriched Uranium,” National Academy of Sciences Report, 2009

The Supply of Medical Radioisotopes series,” Nuclear Energy Agency, 2011

Online Articles and Other References:

A Political Meltdown,” Alison Motluk, Walrus Magazine, April 2011

The Technetium-99m Generator,” Brookhaven National Laboratory

Logistics of Lifesaving: Two Days in the Life of Mo-99,” YouTube video uploaded by Nordion

Molybdenum-99 Fission Radiochemical,” Nordion fact sheet, PDF

Xenon-133 Fission Radiochemical Xenon Gas,” Nordion fact sheet, PDF

NNSA Works to Minimize the use of HEU in Medical Isotope Production,” NNSA Fact Sheet, November 1, 2011

Endangered Isotopes: Where Will Nuclear Medicine Get Its Critical Tool?,” Txchnologist, September 27, 2011

The Heart of Modern Nuclear Medicine: Mo-99 Medical Isotope Production in the United States,” NSA, March 4, 2013


Chronology

1989: Cintichem Reactor, the only domestic supplier of Mo-99 to the United States, is permanently shut down.

1992: The U.S. Department of Energy (DOE) begins an effort to produce Mo-99 in its reactors.

1999: DOE ends its efforts to produce Mo-99 after a solicitation of private companies yields no interest.

2001: Mo-99 shipments to the United States by air are halted temporarily after the September 11 terrorist attacks.

2002: HFR is shut down for 42 days because of reactor operation safety concerns.

2005: Production of Tc-99m generators by Mallinckrodt is shut down in the United States on November 18 because of a product recall. Production is not restarted until April 2006.

2006: NRU reactor is shut down for approximately 6 days because of a technical problem.

2007: NRU reactor is shut down for 24 unplanned days by its regulator to address safety concerns.

2008: HFR is voluntarily shut down in August 2008 after a corrosion problem in the primary cooling system is discovered. The reactor is not scheduled to come back online until February 2009. IRE is shut down in August 2008 after I-131 was unexpectedly vented through a stack. The facility received approval to restart on November 4, 2008. A scheduled 5-day shutdown of NRU Reactor in December 2008 was extended for several additional days. Because HFR was also shut down at the time, there were supply shortages in the United States and Canada.

January 26, 2009: B&W and Covidien sign agreement to develop Mo-99 generation based on aqueous homogeneous reactor technology.

April 29, 2009: TRIUMF and MDS Nordion sign agreement to study feasibility of Mo-99 produced by photo-fission in uranium-238.

January 25, 2010: Babcock & Wilcox awarded $9M by NNSA to develop AHR technology for Mo-99 production, plans to operate by 2014.

December 6, 2010: First LEU-Produced Mo-99 Approved for Patient Use Arrives in U.S. from South Africa

January 25, 2011: Sen. Jeff Bingaman introduces S.99: “American Medical Isotopes Production Act of 2011.”

November 17, 2011: S.99 passes the Senate.

October 15, 2012: In a letter to nuclear medical providers, Mallinckrodt, the pharmecuticals division of Covidien, indicated that they would no longer be supporting the development of the Babcock & Wilcox aqueous homogenous reactor for molybdenum-99 production. B&W suspended design work shortly thereafter.

December 2012: Babcock & Wilcox end their efforts to construct an aqueous homogeneous reactor for medical isotope production.

December 21, 2012: The American Medical Isotope Production Act, which was included in the conference agreement for the National Defense Authorization Act for fiscal year 2013, passes the Senate.

January 2, 2013President Obama signs the National Defense Authorization Act into law, including the American Medical Isotope Production Act.

April 1-4, 2013: Representatives from Flibe Energy attend the 2013 Mo-99 Topical Meeting in Chicago, Illinois. The meeting is sponsored by the National Nuclear Security Administration and hosted by Argonne National Laboratory.Meeting summary.

May 30, 2013: Flibe Energy submits a letter of intent to the Nuclear Regulatory Commission noting their plans to build and operate a liquid-fluoride research reactor that will also produce significant quantities of molybdenum-99.

June 25-27, 2014: Flibe Energy attends the 2014 Mo-99 Topical Meeting in Washington, DC. The meeting is sponsored by the National Nuclear Security Administration and hosted by Argonne National Laboratory. Meeting summary.

September 1-3, 2015: Flibe Energy attends the 2015 Mo-99 Topical Meeting in Boston, MA. The meeting is sponsored by the National Nuclear Security Administration and hosted by Argonne National Laboratory.

April 20, 2016: Flibe Energy and NRG identify the potential for joint collaboration for Mo99 production at the High-Flux Reactor in the Netherlands.

September 2, 2016: Flibe Energy receives authorization from the NNSA under 10 CFR Part 810 to proceed with their joint research with NRG into Mo99 production at the High-Flux Reactor in the Netherlands.

September 11-14, 2016: Flibe Energy attends the 2016 Mo-99 Topical Meeting in St. Louis, MO. The meeting is sponsored by the National Nuclear Security Administration and hosted by Argonne National Laboratory.

December 29, 2016: Flibe Energy receives an export license from the Dutch government which authorizes and enables technical collaboration on the Mo99 project with NRG.

January 30, 2017: Flibe Energy and NRG sign a contract for a molten-salt technology development project wherein Mo99 would be produced from molten salt irradiated in the High-Flux Reactor in the Netherlands.