Page 53 - 2014 Printable Abstract Book
P. 53
(S1001) Biodosimeter Development Process, Progress and Challenges. Lynne M. Wathen, US Dept. of
Health and Human Services, Alexandria, VA
A large-scale radiological or nuclear incident in a large metropolitan setting would result in an
immediate critical need to assess potentially dangerous exposures received by tens of thousands of
individuals to allow for prompt triage and appropriate medical treatment decisions. Measuring the
individual absorbed dose levels will require system architecture or a system of platforms that contains
diverse, integrated diagnostic and dosimetric tools that are accurate and precise. For large-scale incidents,
precision, rapidity, and ease of screening are essential. The Biomedical Advanced Research and
Development Authority (BARDA) within the HHS Office of the Assistant Secretary for Preparedness and
Response coordinates and administers programs for the advanced development and acquisition of
emergency medical diagnostics. The Diagnostics and Medical Devices Division of BARDA, is currently
sponsoring six projects using several detection technologies to demonstrate their varying utility in readily
accessible biological specimens. These projects include a chromosome-damage micronuclei assay,
proteomic and gene expression profiles of blood samples, and electron paramagnetic resonance of incisor
teeth. Human and non-human primate samples have been evaluated and biomarker panels have been
identified. The on-going progress of the projects in their validation efforts will be reviewed. Development
and scientific challenges in achieving sufficient accuracy, specificity and reproducibility to ensure effective
and appropriate use of medical countermeasures will be presented.
(S1002) Aiding Biomarker Development While Implementing Strategies to Minimize Animal Use in
Radiation Biomarker Discovery. Melanie L. Doyle-Eisele; Jeremy Brower, PhD; Waylon Weber, PhD; and
Dunstana Melo, PhD, Lovelace Respiratory Research Institute, Albuquerque, NM
In order to fulfill their mission to protect the public in the event of a radiation exposure The
Biomedical Advanced Research and Development Authority (BARDA) is working with multidisciplinary
teams of researchers to identify and validate biomarkers of absorbed dose. Many of the biomarker studies
have been conducted in rodent species. To further validate their utility in humans, studies were conducted
in nonhuman primates (NHP) exposed to radiation doses which endpoints vary from LD0/60 to LD100/60 for
hematopoietic acute radiation syndrome (h-ARS) model. To conserve use of animals, BARDA conducted
the study at a central location and collected samples for distribution to multiple laboratories where the
samples will be analyzed as part of a single study. To meet the needs of the study, an h-ARS model was
adapted to enable collection of larger amounts of blood (than typical of a standard model) over a wide
range of time points. Because the animals were compromised, adjustments for available blood and
supportive care strategies needed to be optimized. One hundred twenty (120, 60 males and 60 females)
rhesus macaques were exposed to external photon radiation at nominal doses of 0, 2, 4, 6, 8, and 10 Gy.
The irradiation was performed bilaterally using a 6 MV Varian 600c linear accelerator at approximately
0.8 Gy/minute. Clinical signs of h-ARS were monitored a minimum of twice daily through cage-side
observations. Blood samples were collected for hematology and biomarkers on Days -3, 1, 3, 5, and 7
totaling ~77 mL over 10 days (the last collection was performed on the day of necropsy). Supportive care
consisted of once daily oral antibiotics (5 mg/kg Baytril), vitamin (Flintstone Pediatric vitamin with iron),
subcutaneous fluids (when deemed necessary), and a fruit or vegetable each day during observations.
This presentation will describe the biomarker model, the adaptations made to conserve animal use, and
the practical considerations for conducting this type of study. The adaptations enabled successful
51 | P a g e
Health and Human Services, Alexandria, VA
A large-scale radiological or nuclear incident in a large metropolitan setting would result in an
immediate critical need to assess potentially dangerous exposures received by tens of thousands of
individuals to allow for prompt triage and appropriate medical treatment decisions. Measuring the
individual absorbed dose levels will require system architecture or a system of platforms that contains
diverse, integrated diagnostic and dosimetric tools that are accurate and precise. For large-scale incidents,
precision, rapidity, and ease of screening are essential. The Biomedical Advanced Research and
Development Authority (BARDA) within the HHS Office of the Assistant Secretary for Preparedness and
Response coordinates and administers programs for the advanced development and acquisition of
emergency medical diagnostics. The Diagnostics and Medical Devices Division of BARDA, is currently
sponsoring six projects using several detection technologies to demonstrate their varying utility in readily
accessible biological specimens. These projects include a chromosome-damage micronuclei assay,
proteomic and gene expression profiles of blood samples, and electron paramagnetic resonance of incisor
teeth. Human and non-human primate samples have been evaluated and biomarker panels have been
identified. The on-going progress of the projects in their validation efforts will be reviewed. Development
and scientific challenges in achieving sufficient accuracy, specificity and reproducibility to ensure effective
and appropriate use of medical countermeasures will be presented.
(S1002) Aiding Biomarker Development While Implementing Strategies to Minimize Animal Use in
Radiation Biomarker Discovery. Melanie L. Doyle-Eisele; Jeremy Brower, PhD; Waylon Weber, PhD; and
Dunstana Melo, PhD, Lovelace Respiratory Research Institute, Albuquerque, NM
In order to fulfill their mission to protect the public in the event of a radiation exposure The
Biomedical Advanced Research and Development Authority (BARDA) is working with multidisciplinary
teams of researchers to identify and validate biomarkers of absorbed dose. Many of the biomarker studies
have been conducted in rodent species. To further validate their utility in humans, studies were conducted
in nonhuman primates (NHP) exposed to radiation doses which endpoints vary from LD0/60 to LD100/60 for
hematopoietic acute radiation syndrome (h-ARS) model. To conserve use of animals, BARDA conducted
the study at a central location and collected samples for distribution to multiple laboratories where the
samples will be analyzed as part of a single study. To meet the needs of the study, an h-ARS model was
adapted to enable collection of larger amounts of blood (than typical of a standard model) over a wide
range of time points. Because the animals were compromised, adjustments for available blood and
supportive care strategies needed to be optimized. One hundred twenty (120, 60 males and 60 females)
rhesus macaques were exposed to external photon radiation at nominal doses of 0, 2, 4, 6, 8, and 10 Gy.
The irradiation was performed bilaterally using a 6 MV Varian 600c linear accelerator at approximately
0.8 Gy/minute. Clinical signs of h-ARS were monitored a minimum of twice daily through cage-side
observations. Blood samples were collected for hematology and biomarkers on Days -3, 1, 3, 5, and 7
totaling ~77 mL over 10 days (the last collection was performed on the day of necropsy). Supportive care
consisted of once daily oral antibiotics (5 mg/kg Baytril), vitamin (Flintstone Pediatric vitamin with iron),
subcutaneous fluids (when deemed necessary), and a fruit or vegetable each day during observations.
This presentation will describe the biomarker model, the adaptations made to conserve animal use, and
the practical considerations for conducting this type of study. The adaptations enabled successful
51 | P a g e
