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Two Synergistic Pharmacons for Removing Toxic Radionuclides from the Body
IB-2728

APPLICATIONS OF TECHNOLOGY:

Treatment of radionuclide exposure from

ADVANTAGES:

ABSTRACT:

Scientists at Berkeley Lab have developed two active pharmaceutical ingredients for the removal (decorporation) of actinides and lanthanides from the body for treatment of radionuclide exposure. These pharmacons are more effective than diethylenetriaminepentaacetic acid (DTPA), which has been the standard therapy for actinide/lanthanide decorporation since the 1950s. The chelating agents—5-LIO(Me-3,2-HOPO) (5LIO) and 3,4,3-LI(1,2-HOPO) (343LI)—are superior to DTPA in that they can be administered orally (not just by IV infusion or nebulizer); are effective at lower doses; and remove elements in addition to the transuranic radionuclides, e.g., Pu, Am, Cm, from more types of tissue.

Both 5LIO and 343LI were administered to mice 1 and 24 hours after injection of various radionuclides to mimic the clinical circumstances under which these agents would be used following an exposure. They were metabolically stable and removed significant amounts of Pu, U, Np, and Am, according to standard tests for assessing retention in tissue and excretion in feces. On average, the combination of the chelators was 1.5 times more effective than DTPA and reduced radionuclide levels in bone, liver, and kidney—primary areas of deposition. Similar results were also observed in dogs and demonstrate the utility and safety of the agents in a second mammalian species, thus providing evidence required for pharmacons that would be ethically impossible to test in a clinical trial. These are the first compounds in several decades to improve treatment of radionuclide exposure.

DEVELOPMENT STAGE: Preclinical development completed.

STATUS: Published patent application US2010/034266 available at www.wipo.int. Available for licensing or collaborative research.

SEE THESE OTHER BERKELEY LAB TECHNOLOGIES IN THIS FIELD:

Assay to Determine Sensitivity To Radiation, IB-3203

REFERENCE NUMBER: IB-2728

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