Photos placed in horizontal position with even amount of white space between photos and header A Study Comparing the Efficacy of Gamma and X Rays in Biological Research Charles Gus Potter Sandia National Laboratories Sandia National Laboratories is a multimission laboratory managed and operated by National Technology and Engineering Solutions of Sandia, LLC, a wholly owned subsidiary of Honeywell International, Inc., for the U.S. Department of Energys National Nuclear Security Administration under contract DE-NA0003525. SAND NO. 2018-0624 PE There are three general categories of radiological terrorism. Device Type Dispersal Form Economic Effects
Health Effects Comments Radiation Exposure Device (RED) None Low Deterministic effects including acute radiation syndrome (radiation sickness) Could impact thousands; Lethality difficult; No lasting economic impact
Food or Water poisoning Dissolve or mix Medium Serious health effects over large population Not unique Other poisons more readily available RDD for Area Denial Many
High Few (if any) prompt health effects; Slight increased cancer risk Unique aspect of radiological material Cesium contamination can result in considerable consequences. Chernobyl, USSR April 1986 2 Million Ci, Cs-137 Gioania, Brazil, September,1987 70 g Cs-137 resulted in 40 tons of rad-waste Dispersal from medical irradiator source could contaminate a large area.
Range TED Area (sq mi) Population Cancers Fatal 2 rem/1st year 2 10,000 158
0.5 rem/2nd year 7 30,000 5 rem/50 yrs 14 47,000 Range TED Area (sq mi) Population Cancers
The study objective was to demonstrate a source replacement option for medical research irradiators. SNL/LRRI Team, Dr. Bobby Scott, PI Perform comparisons between gamma and X-ray systems for common experiments. o Cells compare relative biological effectiveness (RBE) for different cell lines o Mice bone marrow cell ablation capability o Model mouse data Results published in peer-reviewed journals The 137Cs gamma ray was considered the standard in this research. X = 4.6
2.9 (@ 30%) 1.6 D = absorbed dose of ray standard DX = absorbed dose of X-ray that causes same damage Commercial gamma and X-ray devices were used in the comparison. Gammacell 1000 X-RAD 320 The energy profile of the two devices is quite different. Courtesy of Pete Rowland, Precision X-ray Courtesy of Dan Dorsey, SNL Several assays and cell lines were used in cell experiments. MTT colorimetric assay for cytotoxicity
o Color indicates reduction in metabolic activity o Used in this work to estimate RBE Other common assays used o Cell migration viability by observing migration towards stimulant o Colony formation ability of single cell to form colony o Western blot uses antibodies to detect specific proteins Results of cell experiments indicate capability with increase in dose. Assay Cell Lines X/ Dose Responses Dose Responses Similar? MTT (cytotoxicity)
HBEC-2, HBEC-13, HFL- Yes 1, A549, HeLa, MCF-7 Cell Migration A549, HeLa Yes Colony Formation A549 Yes Western Blot HBEC-2 Yes
RBE Estimates (cytotoxicity) o Normal Cells: 1.5 (HBEC-13) 1.6 (HBEC-2), HVL=1 mm Cu o Cancer Cells: 1.2 (HeLa) 1.5 (A549), HVL=3.7 mm Cu Two studies were performed to determine bone marrow ablation effectiveness. Bone Marrow Transplantation o Used for leukemia, solid tumors, other metabolic diseases. o High-dose therapy used to ablate bone marrow. o Syngeneic or allogeneic bone marrow is grafted. Incomplete ablation host marrow out-competes donor Two studies, both irradiators used in each o X-Rad 320: HVL = 3.7 mm Cu Whole-body irradiation did not completely ablate. Study 1: Whole-body irradiation only (designed for RBE = 1.3) o Bone marrow & spleen cell depletion o Body weight loss & recovery
o Reconstitution of spleen & bone marrow 6 weeks Gammacell 1000 X-Rad 320 2.03 Gy 1.56 Gy 4.01 Gy 3.09 Gy 6.0 Gy 4.62 Gy Bone marrow and spleen reconstituted.
Study 2: Whole-body irradiation & transplant o Body weight loss and recovery o Reconstitution of spleen & bone marrow 6 weeks Gammacell 1000 X-Rad 320 2.03 Gy 1.56 Gy 4.01 Gy 3.09 Gy 6.0 Gy
4.62 Gy Additional dose is likely required for ablation and splenocyte killing. Bone marrow ablation was similar at each dose level. Viable splenocytes at 24 hrs and 6 weeks significantly lower for gamma vs. X rays RBE for splenocyte killing less than 1.3 Allogeneic bone marrow engraftment unsuccessful for X rays. Splenocyte modeling confirms need for additional dose. Models developed to predict if higher doses would successfully ablate spleen tissue. Mouse study 1 data modeled. Results: o RBE for splenocytes closer to 0.94 o More data at higher doses needed Both irradiators experienced maintenance issues during research. X-RAD 320 o Room temperature buildup o Maintenance costs higher than Gammacell o Throughput may be issue in large transfusion programs
Gammacell 1000 o Aging units also expensive to maintain Publications B. R. Scott, J. Hutt, Y. Lin, M. T. Padilla, K. M. Gott, and C. A. Potter. Biological microdosimetry based on radiation cytotoxicity data. Radiation Protection Dosimetry, 153(4): 417-424, 2013. B. R. Scott, K. M. Gott, C. A. Potter, and J. Wilder. A comparison of in vivo cellular responses to Cs-137 gamma rays and 320-kV X rays. Dose Response, 11:444-459, 2013. B. R. Scott and C. A. Potter. Stochastic threshold exponential (TE) model for hematopoetic tissue reconstitution deficit after radiation damage. Dose Response, 12:415-428, 2014.
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