SPECIAL NOTICE
A -- Development of Novel Chelating Agents for the Treatment of Internal Contamination with Radionuclides
- Notice Date
- 2/9/2004
- Notice Type
- Special Notice
- Contracting Office
- Department of Health and Human Services, Center for Disease Control and Prevention, Procurement and Grants Office (Atlanta), 2920 Brandywine Road, Room 3000, Atlanta, GA, 30341-4146
- ZIP Code
- 30341-4146
- Solicitation Number
- Reference-Number-0001RFIDTPA
- Response Due
- 3/12/2004
- Archive Date
- 4/12/2004
- Point of Contact
- Peter Penny, Contract Specialist, Phone 770-488-1115, Fax 770-488-2777, - Lorenzo Falgiano, Contract Specialist, Phone (770) 488-2629, Fax (770) 488-2670,
- E-Mail Address
-
pmp7@cdc.gov, ljf5@cdc.gov
- Description
- The Office of the Assistant Secretary for Public Health Emergency Preparedness is seeking capability statements from organizations with the expertise to develop, test, and manufacture novel chelating agents for the treatment of internal contamination with radionuclides. Chelating agents are compounds that react with metals to form stable ionic complexes, facilitating urinary clearance of the metal-chelator complex. The elimination of chelated metals from the body is termed decorporation. Decorporation is the goal of chelation therapy. Calcium (Ca-) DTPA and Zinc (Zn-) DTPA are chelating agents currently used to treat internal contamination with transuranic elements of the actinide series. Military and civilian populations are at risk of internal exposure to particulate transuranic radioactive material from the detonation of radiological dispersion devices (RDD's or ?dirty bombs?), as radioactive fallout from nuclear weapons, and as a consequence of nuclear or radiological accidents. Internalization of particulate radioactive material occurs via inhalation or ingestion or through contamination of open wounds. The radionuclides in these particles are then absorbed, transported via the blood, and ultimately incorporated into physiologically compatible organs such as bone and liver in a time-dependent manner. This process constitutes a health hazard because of the continuous emission of radioactivity to radiosensitive tissues and subsequent development of cell death, organ dysfunction, fibrosis, and malignancy. Ca- and Zn-DTPA, mentioned above, have been used under IND protocols since the 1960?s to treat internal contamination with transuranic isotopes. The U.S. Food and Drug Administration (FDA) has actively collected and reviewed data pertaining to the clinical use of Ca- and Zn-DTPA and has reached the conclusion that the drugs are safe and effective for the treatment of internal contamination with certain transuranic radionuclides (plutonium, americium, and curium). Although insufficient clinical data exist, Ca- and Zn-DTPA may also be effective in chelating thorium, californium, and other elements in the actinide series. Ca- and Zn-DTPA have significant limitations, however. These agents are hydrophilic salts with poor oral bioavailability (approximately 3%) that must be administered intravenously or via aerosol. They are ineffective chelators of the actinide elements uranium and neptunium and cannot solubilise plutonium hydroxides at physiological pH or remove plutonium from bone salt once it has been fixed. Their active ligand, DTPA, is not specific for metals of high ionic charge, and the less potent Ca- and Zn- chelates must be used to avoid hypocalcaemia and depletion of essential divalent metal ions. Most significantly, Ca- and Zn-DTPA do not have activity against other radioisotopes of strategic concern, including cobalt-60, strontium-90, and iridium-192. The following characteristics are desirable in candidate novel chelating agents: 1) The ligand should form a stable chemical complex with the radioisotope in question. 2) The complex formed should be specific for the radioisotope and have little affinity for endogenous cations such as Ca+2, Mg+2, Zn+2, etc. 3) The ligand should be able to compete successfully with endogenous ligands whether the latter be in blood or in the systemic target tissues, e.g., liver and bone. 4) The ligand should have a similar physiological dilution space as that of the radioisotope in question. 5) The radioisotope-ligand complex should be a water-soluble, freely diffusible complex that is readily excreted (lipophilic prodrugs targeting specific organs which are then metabolized to the more diffusible forms excretable in urine may have clinical applications in certain settings). 6) The ligand should be degraded or metabolized slowly in vivo compared to the excretion rate. Otherwise, larger doses of ligand are required. 7) The ligand should have a low toxicity relative to the dose required for efficient decorporation. Additionally, in an event where a large number of individuals may have sustained internal contamination with particulate radionuclides, the ability to administer chelation therapy orally would provide significant operational advantages, both in terms of the speed and sustainability of the response. The respondent should consider the following elements: 1) As an issue of health security, the U.S. government is seeking to encourage domestic manufacturing of novel chelating agents and other radiological countermeasures. 2) Documented history of successful development and licensure of drugs for human use in the United States or Europe is advantageous. 3) The research and development process and proposed manufacturing facilities will need to satisfy regulatory requirements of the FDA. Interested organizations should submit capability statements that contain descriptions of their capabilities and interests as well as their potential development and production plans including a description of their potential or available manufacturing capabilities. Any perceived barriers ? scientific and financial ? to the conduct of this work should also be indicated. The capability statements, along with any supporting documentation, should not exceed 10 pages. Capability statements and letters of interest will be kept confidential and will help in determining the need for an RFP to support research and development activities and in assembling a potential source list for distribution of any resultant RFP. This is not a Request for Proposals and does not commit the Government to award a contract now or in the future. Submission of any information based on this request for information is purely voluntary. Please specify, if applicable, the small business size status of your company (See Federal Acquisition Regulations, Part 19). No solicitation is available at this time. No collect calls will be accepted. Submit your response via email only to Pete Penny, at pmp7@cdc.gov, Contract Specialist.
- Record
- SN00518672-W 20040211/040209215030 (fbodaily.com)
- Source
-
FedBizOpps.gov Link to This Notice
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