Without warning, a major earthquake and subsequent tsunami hit Japan in March 2011. Damage was significant at almost every level, impacting people and the environment. Shortly thereafter, a core meltdown at the Fukushima Daiichi nuclear plant—the largest nuclear event since the Chernobyl disaster in 1986—intensified the situation. Almost immediately concern arose about the many health risks associated with nuclear power plant accidents.
A disaster of such magnitude has brought new focus and urgency to studying the effects of radiation, protection, and therapy against radiation and radionuclides. Research into many relevant areas was suddenly in the spotlight:
- Radiation-induced damage, including mutagenesis and carcinogenesis
- Radiobiology and radiation exposure models in general, assessing the biological effects of internally deposited radionuclides and protection from their radiation, and including mitigators such as targeted drugs
- Biodosimetry methods to measure levels of radiation exposure and the effects of radiation both on earth and in space, including risk assessment and epidemiology;
- Bystander effects and adaptive responses
- Public policy and disaster planning – acute radiation syndrome and radiation effects
In the event of Fukushima-type incident or a “dirty” bomb detonation, providing antidotes or other treatments to mass populations would quickly be of highest priority. An oral product that could be self-administered would be ideal in such situations. Currently, the only decorporation treatments (which eliminate toxic substances from the body) available for use following human contamination with radionuclides are formulations of diethylenetriamine pentaacetate (DTPA or pentetate). DTPA chelates and thereby aids in the excretion of radionuclides such as americium, curium, and plutonium from the body. Today, DTPA can only be administered intravenously or via inhalation. This is a major drawback considering the logistical challenge of administering drugs intravenously to a potentially large number of individuals in a mass casualty setting.
Fortunately, with support from the U.S. National Institutes of Health (NIH), SRI International’s work has led to a novel, orally bioavailable formulation of DTPA that is nearing human clinical testing. Our plan is to provide oral tablets that could be used immediately to treat millions of people if necessary, unlike just a few tens to hundreds to thousands of patients who could be treated with current intravenous products.
At SRI International, researchers are pursuing advances in several of these areas, typically with collaborators in academia, national laboratories, other nonprofit research organizations, and biotechnology or pharmaceutical companies.
DTPA research carried out by SRI and other organizations exploring new chelating agents builds on many years of previous work. Further, this work begins to establish a foundation for the successful development of new and improved ways to deal with serious exposure to radiation, whether the result of a laboratory accident, a nuclear energy plant disaster, or a terrorist act. The irony is that we hope these advances in the field will never be needed. Nonetheless, we must be ready, and we hope that our efforts will contribute in at least some small way to providing comfort that help will be available when and if it is needed.
Adapted in part from: Moos WH, Shankar, GN. 2012. Radiation Drugs – A Hot Topic. Drug Development Research 73:229-231.
This project has been funded in part or in full by SRI International together with federal funds from NIAID/NIH/DHHS under contract nos. HHSN266200500047C and HHSN272201000029C.
