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中文摘要
翻译
本申请是对RFA-A1-06-030《用于辐射/核的放射性核素脱腐剂》的响应
英文摘要
This application is in response to RFA-A1-06-030, Radionuclide Decoproration Agents for Radiation/Nuclear Emergencies: Project BioShield (R01). We propose to further develop a series of amphipathic, orally administered, polyaminocarboxylic (PACA) chelators. These are based on triethylenetetraminehexaacetic acid (TT) and are related to diethylenetriamine-pentaacetic acid (DTPA). The orally administered amphipathic TT chelators are very effective for the elimination of systemic deposits of americium and plutonium)and some transition metals. They also have broad chemical binding affinities for a range of potentially toxic metals. We propose 3 studies. 1) To perform pharmacokinetic (PK) studies to determine the absorption, distribution, metabolism and excretion of the TT chelators as a function of their amphipathic properties. C-14 labeled compounds will be synthesized and tested using established PK methods. These data.will help optimize chelator design and dose range profiles. 2) To determine the binding stabilities for a range of metals and determine the ability of the amphipathic TT chelators to extract these metals in vitro. .. Liver and erythrocyte assays will determine the binding and extraction of metals to include uranium, cobalt, strontium and cerium. These data will help optimize chelator design for various metals for the in vivo studies. 3) To determine the ability of the orally administered TT chelators, to promote excretion of internally incorporated metals. The same metals as used in study 2 will be used (U, Co, Sr, Ce) and these represent different chemical classes (e.g. actinide, transition metal, alkaline earth metal and lanthanide) and their radioactive isotopes are potential components of a radiological dispersion device. Effective doses of injected DTPA will be used as a comparison control. Further development may include specific radionuclide efficacy Jtudies, perhaps to include exposures by different routes (e.g. inhalation, wounds). Regulatory compliant toxicity and safety studies should to be conducted. Because the pharmacology and toxicology of PACA chelators, such as DTPA and EDTA, are quite well understood, the development pathway of the related TT- based chelators may proceed rapidly.
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Pharmacological properties of orally available, amphipathic polyaminocarboxylic acid chelators for actinide decorporation.
用于锕系元素修饰的口服两亲性聚氨基羧酸螯合剂的药理学特性。
DOI: 10.1097/hp.0b013e3181bfb99b
发表时间: 2010
期刊: Health physics
影响因子: 2.2
作者: [Miller,ScottC, Wang,Xuli, Bowman,BethM]
通讯作者: Bowman,BethM
AMPHIPATHIC ORAL CHELATORS AND RADIONUCLIDE CONTAMINATION
  • 批准号:
    7267886
  • 项目类别:
  • 资助金额:
    $67.5万
  • 财政年份:
    2006
  • 负责人:
    SCOTT C. MILLER
  • 依托单位:
MECHANISMS OF SKELETAL RECONSTITUTION AFTER LACTATION
  • 批准号:
    6532968
  • 项目类别:
  • 资助金额:
    $22.5万
  • 财政年份:
    1998
  • 负责人:
    SCOTT C. MILLER
  • 依托单位:
MECHANISMS OF SKELETAL RECONSTITUTION AFTER LACTATION
  • 批准号:
    2691106
  • 项目类别:
  • 资助金额:
    $18.68万
  • 财政年份:
    1998
  • 负责人:
    SCOTT C. MILLER
  • 依托单位:
MECHANISMS OF SKELETAL RECONSTITUTION AFTER LACTATION
  • 批准号:
    6171446
  • 项目类别:
  • 资助金额:
    $19.45万
  • 财政年份:
    1998
  • 负责人:
    SCOTT C. MILLER
  • 依托单位:
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