Page 345 - 2014 Printable Abstract Book
P. 345
protein expression patterns in plasma subfractions from radiated versus non-irradiated mice and the
development of a panel of candidate biomarkers for the human assessment of radiation exposure.
(PS6-34) Pharmacokinetic evaluation and dose dependence of efficacy in americium contaminated
1
beagle dogs after daily treatment with oral and intravenous formulations of Zn-DTPA. Gita N. Shankar ;
2
1
Carol E. Green ; and Ray A. Guilmette , SRI International, Menlo Park, CA and Lovelace Respiratory
1
2
Research Institute, Albuquerque, NM
The drug of choice for removing radionuclides like americium and plutonium from a contaminated
person, a process called decorporation, is diethylenetriamine pentaacetic acid (DTPA). Because DTPA has
poor oral bioavailability, the current approved methods of drug delivery are intravenous or solution
nebulization. To facilitate decorporation for large groups, we are developing orally bioavailable
formulations of DTPA. In this study, we evaluated pharmacokinetic parameters and dose dependence in
americium contaminated dogs after treatment with a novel tablet formulation of Zn chelate form of DTPA
(SRI-DTPA). The objective of this work was to study the dose dependence of the efficacy of SRI’s oral tablet
formulation of Zn-DTPA in beagle dogs following administration of a single intravenous (IV) dose of
Americium-241. An additional objective of this study was to determine basic pharmacokinetic parameters
of DTPA. Administration of 15 mg/kg Zn-DTPA by the IV route resulted in high plasma concentrations
which were eliminated with an average t1/2 of about 1 hr, Cl of 155 mg/kg/hr and Vss of 120 ml/kg. Zn-
DTPA was rapidly absorbed after oral administration of SRI’s proprietary tablet formulation, with a mean
Tmax of about 1-2 hr. The Cmax and AUCinf increased with dose level in the groups administered a single daily
dose of Zn-DTPA. As expected, treatment with ½ tablet twice a day resulted in Cmax values that was similar
those obtained after administration of a single daily dose of ½ tablet QD. The t1/2 of DTPA after oral
administration was approximately two hr in all groups. This project has been funded in full with federal
funds from NIAID/NIH/DHHS under contract no. HHSN266200500029C.
1
(PS6-36) A new rat model of neutron-gamma irradiation-induced lung pneumonitis. Susan Braunhut ;
1
2
1
1
2
Abiche Dewilde ; John Moulder ; Brian Fish ; and Mark Tries , University of Massachusetts, Lowell, MA
2
and Medical College of Wisconsin, Milwaukee, WI
Our nation is at risk to experience an attack or accidental release of neutron-gamma radiation in
a theater of operations or at home leaving large numbers of irradiated civilians and/or soldiers needing
mitigating treatments to ensure their survival and minimize long-term effects of the radiation exposure.
First responders will need protectors to enter areas of residual radiation contamination to assist survivors
and biomarkers will be needed to triage survivors, reflecting received dose. Biomarkers, mitigators and
protectors developed using low linear energy transfer (LET) radiation sources (gamma, x-ray), have rarely
been confirmed using neutron-gamma irradiation. Nuclear devices will produce four types of radiation:
neutrons, gamma rays, beta particles and alpha particles and fundamental research is lacking on unique
high LET induced chemical alterations, neutron activation and nuclear transmutation of biological
substrates in cells and tissues. U Mass Lowell is one of only 26 US universities with an operating nuclear
research reactor and we have recently designed and built a one-of-a-kind monorail system to safely
transport animals to the beam port for neutron-gamma studies that use high LET radiation likely to be
experienced from accidental or malicious neutron gamma device detonation. We are developing a rat
343 | P a g e
development of a panel of candidate biomarkers for the human assessment of radiation exposure.
(PS6-34) Pharmacokinetic evaluation and dose dependence of efficacy in americium contaminated
1
beagle dogs after daily treatment with oral and intravenous formulations of Zn-DTPA. Gita N. Shankar ;
2
1
Carol E. Green ; and Ray A. Guilmette , SRI International, Menlo Park, CA and Lovelace Respiratory
1
2
Research Institute, Albuquerque, NM
The drug of choice for removing radionuclides like americium and plutonium from a contaminated
person, a process called decorporation, is diethylenetriamine pentaacetic acid (DTPA). Because DTPA has
poor oral bioavailability, the current approved methods of drug delivery are intravenous or solution
nebulization. To facilitate decorporation for large groups, we are developing orally bioavailable
formulations of DTPA. In this study, we evaluated pharmacokinetic parameters and dose dependence in
americium contaminated dogs after treatment with a novel tablet formulation of Zn chelate form of DTPA
(SRI-DTPA). The objective of this work was to study the dose dependence of the efficacy of SRI’s oral tablet
formulation of Zn-DTPA in beagle dogs following administration of a single intravenous (IV) dose of
Americium-241. An additional objective of this study was to determine basic pharmacokinetic parameters
of DTPA. Administration of 15 mg/kg Zn-DTPA by the IV route resulted in high plasma concentrations
which were eliminated with an average t1/2 of about 1 hr, Cl of 155 mg/kg/hr and Vss of 120 ml/kg. Zn-
DTPA was rapidly absorbed after oral administration of SRI’s proprietary tablet formulation, with a mean
Tmax of about 1-2 hr. The Cmax and AUCinf increased with dose level in the groups administered a single daily
dose of Zn-DTPA. As expected, treatment with ½ tablet twice a day resulted in Cmax values that was similar
those obtained after administration of a single daily dose of ½ tablet QD. The t1/2 of DTPA after oral
administration was approximately two hr in all groups. This project has been funded in full with federal
funds from NIAID/NIH/DHHS under contract no. HHSN266200500029C.
1
(PS6-36) A new rat model of neutron-gamma irradiation-induced lung pneumonitis. Susan Braunhut ;
1
2
1
1
2
Abiche Dewilde ; John Moulder ; Brian Fish ; and Mark Tries , University of Massachusetts, Lowell, MA
2
and Medical College of Wisconsin, Milwaukee, WI
Our nation is at risk to experience an attack or accidental release of neutron-gamma radiation in
a theater of operations or at home leaving large numbers of irradiated civilians and/or soldiers needing
mitigating treatments to ensure their survival and minimize long-term effects of the radiation exposure.
First responders will need protectors to enter areas of residual radiation contamination to assist survivors
and biomarkers will be needed to triage survivors, reflecting received dose. Biomarkers, mitigators and
protectors developed using low linear energy transfer (LET) radiation sources (gamma, x-ray), have rarely
been confirmed using neutron-gamma irradiation. Nuclear devices will produce four types of radiation:
neutrons, gamma rays, beta particles and alpha particles and fundamental research is lacking on unique
high LET induced chemical alterations, neutron activation and nuclear transmutation of biological
substrates in cells and tissues. U Mass Lowell is one of only 26 US universities with an operating nuclear
research reactor and we have recently designed and built a one-of-a-kind monorail system to safely
transport animals to the beam port for neutron-gamma studies that use high LET radiation likely to be
experienced from accidental or malicious neutron gamma device detonation. We are developing a rat
343 | P a g e
