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CHELATING AGENTS
Title: PRINCIPAL INVESTIGATOR
Phone: (904) 462-1210
MOST CHELATING AGENTS THAT ARE EFFECTIVE IN DECORPORTATION RADIONUCLIDES FROM PATIENTS EXPOSED TO THEM ARE NOT EFFECTIVE WHEN ADMINISTERED ORALLY. DTPA IS AN EXAMPLE OF ACHELATING AGENT WHICH HAS TO BE GIVEN I.V. ON A DAILY BASIS TO REMOVE EFFECTIVELY PLUTONIUM FROM THE SKELETON AND OTHER SOFT TISSUES. ALTHOUGH VARIOUS LIPOPHILIC CHELATING AGENTS HAVE BEEN SYNTHESIZED, NONE OF THEM HAVE BEEN EFFECTIVE ORALLY, AND DATA ON THEIR ORAL BIOAVAILABILITY HAVE NOT BEENREPORTED. THIS PROPOSAL SEEKS TO IMPROVE THE GASTROINTESTINAL (G.I.) ABSORPTION OF EFFECTIVE CHELATING AGENTS. ACCORDING TO ONE APPROACH, AN ACTIVATED ESTER OF DTPA WILL BE CONSIDERED. SUCH AN ESTER SHOULD DELIVER DTPA ACROSS THE G.I. MEMBRANE AND HYDROLYZE TO DTPA IN THE BLOOD STREAM. THE SECOND APPROACH WILL INVESTIGATE FORMATION OF LIPOPHILIC ION-PAIRS BETWEEN DTPA AND A UNIQUE CATIONIC COMPOUND. THE THIRD APPROACH WILL EXAMINE A LIPOPHILIC AMINOTHIOL CHELATING AGENT, AND COMPARE IT TO A LIPOPHILIC AMIDOTHIOL WHICH IS DESIGNED TO CONVERT TO A POLAR CHELATINGAGENT ONCE IN THE BLOOD. AFTER SYNTHESIS OF THE THREE CHELATING AGENTS, AND DEVELOPMENT OF SUITABLE ANALYTICAL SYSTEMS, STABILITY AND RELEASE OF THE CORRESPONDING POLAR AGENTS WILL BE STUDIED IN BIOLOGICAL MATERIALS IN VITRO. THE ORAL ABSORPTION OF THESE CHELATING AGENTS WILL BE EXAMINED IN THE RAT BY COMPARING BLOOD LEVELS AFTER I.V. ANDORAL TREATMENTS.
* Information listed above is at the time of submission. *