Caldera aims to develop an inexpensive, stable, selective, decorporation (decorp) agent for cesium-137 (Cs-137). Cs-137 is easily obtainable by terrorists and treatments for exposures are Project Bioshield priorities for use in radiation/nuclear emergencies, high priority for DHHS / NIH / NIAID / DAIT, and a critical need for the Strategic National Stockpile (SNS). Caldera's agent will select for Cs over potassium (K), sodium (Na), and other elements that are essential for human health. Current treatments are non-selective and must be used under strict clinical supervision. Selectivity is needed because Na and K are more prevalent than Cs in the body; non-selective decorp agents are swamped by Na and K. Na, K, and Cs have similar properties, so selective treatments are traditionally very difficult to develop. Agents such as Prussian Blue (PB) are current treatments for Cs exposure; however PB only binds Cs from the gastrointestinal tract/GI. DTPA analogs have been approved by the FDA for treatment of plutonium, americium, and curium, but they are in intravenous forms, so are difficult to administer in response to mass exposure. Caldera's approach focuses on chelating radioactive Cs in blood and muscle that has been absorbed systemically from all exposure routes (oral, dermal, inhaled); There are no decorp agents to selectively remove Cs from the bloodstream and musculature. Caldera will use XRpro(r), a high throughput screening (HTS), label-free, x-ray fluorescence (XRF) technology to produce selective decorp agents for Cs and other radioisotopes. XRpro(r) protocols, instruments, microarrays, and novel ligands increase the signal and decrease the noise for measuring Cs, increasing the likelihood that Phase I will result in novel, selective Cs- decorp agents.
Public Health Relevance Statement: Public Health Relevance: Caldera aims to develop an inexpensive, stable, selective, decorporation (decorp) agent for cesium-137 (Cs-137). Cs-137 is easily obtainable by terrorists and treatments for exposures are Project Bioshield priorities for use in radiation/nuclear emergencies, high priority for DHHS / NIH / NIAID / DAIT, and a critical need for the Strategic National Stockpile (SNS). Caldera's agent will select for Cs over potassium (K), sod ium (Na), and other elements that are essential for human health. Current treatments are non-selective and must be used under strict clinical supervision.
NIH Spending Category: Biodefense; Biotechnology; Emerging Infectious Diseases; Infectious Diseases
Project Terms: Adherence (attribute); analog; Animals; base; Beryllium; Binding (Molecular Function); Bioshield; Blood; Blood Circulation; Breathing; Calibration; Cells; Cesium; Chelating Agents; Chemical Structure; Chemistry; Clinical; companion diagnostics; Crown Ethers; Data; Data Display; Dermal; Development; Dose; Emergency Situation; FDA approved; Fluorescence; Gastrointestinal tract structure; Grant; Health; high throughput screening; Human; IACUC; in vivo; Industry; instrument; instrumentation; interest; Intravenous; Kinetics; Label; Lead; Libraries; Ligands; Ligation; Measures; Muscle; National Institute of Allergy and Infectious Disease; Nature; Noise; novel; Nuclear; Oral; Pentetic Acid; Pharmaceutical Preparations; Phase; Plutonium; Potassium; Property; Protocols documentation; Prussian blue; Radiation; Radioactive; Radioisotopes; Rattus; response; Route; Salts; Sampling; screening; Sequence Homology; Signal Transduction; Sodium; Strontium; Strontium-90; Structure-Activity Relationship; Supervision; Technology; Testing; Therapeutic; Toxic effect; United States National Institutes of Health
