Page 330 - 2014 Printable Abstract Book
P. 330
WAG/RijCmcr at 9-10 weeks of age) were randomized into 2 groups: (i) no irradiation (control) (ii) a lethal
dose of 15 Gy to the thorax to include the whole volume of both lungs. The lungs were imaged in vivo at
1, 2, 3 and 4 weeks after irradiation using 99m Tc-duramycin (DU) as a SPECT probe of pulmonary apoptosis.
Subsequently relative pulmonary blood flow was measured by 99m Tc-macroaggregated albumin (MAA)
SPECT. The lung region was identified in the DU SPECT volume using the MAA lung volume to define the
lung boundaries. Total activity within the DU lung volume was determined as well as DU/MAA signal per
voxel within the lung volume. Results: A lethal 15 Gy dose of radiation to the lungs increased the DU SPECT
signal in the thorax by 75% at 2 and 39% at 3 weeks (n>3 rats/group). The mean DU/MAA ratio from the
total lung volume was >2 fold in the irradiated rats (n=4) as compared to unirradiated controls (n=8) at 2
weeks (P = 0.002). Our results indicate that composite indices obtained by noninvasive SPECT imaging that
can be readily translated to the clinic can detect lethal radiation-pneumonitis as early as 2 weeks after
irradiation. Funding: NIH/NIAID 1R01AI101898-01, 1U01AI107305-01 and the Dept. of Radiation
Oncology, Medical College of Wisconsin.
(PS6-10) A multi-parameter biodosimetry tool with peripheral blood cell counts - the HemoDose
4;2
1
1;2
3
approach. Shaowen Hu ; William F. Blakely ; and Francis A. Cucinotta , USRA, Houston, TX ; NASA JSC,
2
Houston, TX ; Uniformed Services University of the Health Sciences, Armed Forces Radiobiology Research
Institute, Bethesda, MD ; and University of Nevada, Las Vegas, NV
4
3
There are continuous concerns about the possibility of the occurrence of nuclear and radiological
terrorism or accidents that may result in mass casualties in densely populated areas. To guide medical
personnel in their clinical decisions for effective medical management and treatment of the exposed
individuals, biomarkers are usually applied to examine radiation-induced biological changes to assess the
severity of radiation injury. Among these the peripheral blood cell counts are traditionally regarded as the
most practical and rapid diagnostic indicators. This is due to the facts that the hematopoietic system is
the most vulnerable part of the human body to radiation damage, and the time-dependent changes of
lymphocyte, granulocyte, and platelet concentration in peripheral blood after exposure are highly dose-
dependent. Based upon years of physiological and pathophysiological investigation of mammalian
hematopoietic systems, and rigorous coarse-grained bio-mathematical modeling and validation on
species from rodent, to dog, non-human primate, and human, we have developed a multi-parameter
computational tool HemoDose, which can use single or serial granulocyte, lymphocyte, leukocyte, or
platelet counts after exposure to estimate the absorbed doses of adult victims very rapidly and accurately.
Some patient data from historical accidents are utilized as examples to demonstrate the capabilities of
these tools as a rapid point-of-care diagnostic or centralized high-throughput assay system in a large-scale
radiological disaster scenario. Importantly, this HemoDose approach establishes that robust correlations
between the absorbed doses and victim's various types of blood cell counts exist not only in the early time
window (1 or 2 days), but also in the very late phase (up to 4 weeks) after exposure. Disclaimer. The views
expressed do not necessarily represent those of the Universities Space Research Association, the Armed
Forces Radiobiology Research Institute, the Uniformed Services University of the Health Sciences, the
University of Nevada, the U.S. Department of Defense, or National Aeronautics and Space Administration.
328 | P a g e
dose of 15 Gy to the thorax to include the whole volume of both lungs. The lungs were imaged in vivo at
1, 2, 3 and 4 weeks after irradiation using 99m Tc-duramycin (DU) as a SPECT probe of pulmonary apoptosis.
Subsequently relative pulmonary blood flow was measured by 99m Tc-macroaggregated albumin (MAA)
SPECT. The lung region was identified in the DU SPECT volume using the MAA lung volume to define the
lung boundaries. Total activity within the DU lung volume was determined as well as DU/MAA signal per
voxel within the lung volume. Results: A lethal 15 Gy dose of radiation to the lungs increased the DU SPECT
signal in the thorax by 75% at 2 and 39% at 3 weeks (n>3 rats/group). The mean DU/MAA ratio from the
total lung volume was >2 fold in the irradiated rats (n=4) as compared to unirradiated controls (n=8) at 2
weeks (P = 0.002). Our results indicate that composite indices obtained by noninvasive SPECT imaging that
can be readily translated to the clinic can detect lethal radiation-pneumonitis as early as 2 weeks after
irradiation. Funding: NIH/NIAID 1R01AI101898-01, 1U01AI107305-01 and the Dept. of Radiation
Oncology, Medical College of Wisconsin.
(PS6-10) A multi-parameter biodosimetry tool with peripheral blood cell counts - the HemoDose
4;2
1
1;2
3
approach. Shaowen Hu ; William F. Blakely ; and Francis A. Cucinotta , USRA, Houston, TX ; NASA JSC,
2
Houston, TX ; Uniformed Services University of the Health Sciences, Armed Forces Radiobiology Research
Institute, Bethesda, MD ; and University of Nevada, Las Vegas, NV
4
3
There are continuous concerns about the possibility of the occurrence of nuclear and radiological
terrorism or accidents that may result in mass casualties in densely populated areas. To guide medical
personnel in their clinical decisions for effective medical management and treatment of the exposed
individuals, biomarkers are usually applied to examine radiation-induced biological changes to assess the
severity of radiation injury. Among these the peripheral blood cell counts are traditionally regarded as the
most practical and rapid diagnostic indicators. This is due to the facts that the hematopoietic system is
the most vulnerable part of the human body to radiation damage, and the time-dependent changes of
lymphocyte, granulocyte, and platelet concentration in peripheral blood after exposure are highly dose-
dependent. Based upon years of physiological and pathophysiological investigation of mammalian
hematopoietic systems, and rigorous coarse-grained bio-mathematical modeling and validation on
species from rodent, to dog, non-human primate, and human, we have developed a multi-parameter
computational tool HemoDose, which can use single or serial granulocyte, lymphocyte, leukocyte, or
platelet counts after exposure to estimate the absorbed doses of adult victims very rapidly and accurately.
Some patient data from historical accidents are utilized as examples to demonstrate the capabilities of
these tools as a rapid point-of-care diagnostic or centralized high-throughput assay system in a large-scale
radiological disaster scenario. Importantly, this HemoDose approach establishes that robust correlations
between the absorbed doses and victim's various types of blood cell counts exist not only in the early time
window (1 or 2 days), but also in the very late phase (up to 4 weeks) after exposure. Disclaimer. The views
expressed do not necessarily represent those of the Universities Space Research Association, the Armed
Forces Radiobiology Research Institute, the Uniformed Services University of the Health Sciences, the
University of Nevada, the U.S. Department of Defense, or National Aeronautics and Space Administration.
328 | P a g e
