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Abstract
Purpose: In a significant nuclear event, hundreds of thousands of individuals will require rapid triage for absorbed radiation to ensure effective medical treatment and efficient use of medical resources. We are developing a rapid screening method to assess whether an individual received an absorbed dose of ≥2 Gy based on the analysis of a specific panel of blood proteins in a fingerstick blood sample.
Materials and methods: We studied a data set of 1051 human blood samples obtained from radiotherapy patients, normal healthy individuals, and several special population groups. We compared the findings in humans with those from irradiation studies in non-human primates (NHPs).
Results: We identified a panel of three protein biomarkers, salivary alpha amylase (AMY1), Flt3 ligand (FLT3L), and monocyte chemotactic protein 1 (MCP1), which are upregulated in human patients receiving fractionated doses of total body irradiation (TBI) therapy as a treatment for cancer. These proteins exhibited a similar radiation response in NHPs after single acute or fractionated doses of ionizing radiation.
Conclusion: Our work provides confidence in this biomarker panel for biodosimetry triage using fingerstick blood samples and in the use of NHPs as a model for irradiated humans.
Disclosure statement
The authors have no financial and/or business interest that may be affected by the research reported in this paper.
Additional information
Funding
Notes on contributors
Robert P. Balog
Robert P. Balog received his PhD in BioMedical Engineering from the University of Texas, Southwestern Medical Center in 2004 and spent 14 years at SRI International as a program director. His research interests focus on the discovery of predictive in vitro diagnostic biomarkers and the development of distributed diagnostic platforms. Dr. Balog served as a Co-PI for this work.
Rowena Bacher
Rowena Bacher received her MS in Biology from California State University, Fresno and specialized in biomarker discovery and developing novel immunoassays during her 8 years at SRI. Her current research interests focus on utilizing next-gen sequencing for pathogen detection.
Polly Chang
Polly Chang received her Ph.D. in Biophysics from the University of California, Berkeley in 1991. She is currently the senior director of Molecular and Genetic Toxicology at SRI International and is actively engaged in the field of radiation biology coupled with product development of medical countermeasures for radiation protection. Dr. Chang served as a Co-PI for this work.
Michael Greenstein
Michael Greenstein received his PhD in Physics from the University of Illinois-Champaign Urbana in 1981, and has worked on medical device since 1990, including ultrasound imaging, Immunoassay and Molecular Diagnostic systems. His research and development interests are focused on Point of Care medical devices.
Songeeta Jammalamadaka
Songeeta Jammalamadaka received her MS in Bioengineering from Tufts University and has worked at SRI since 2009 in the area of assay development and medical device engineering. She served as system engineer for writing requirements and specifications and is the lead usability researcher on this radiation biodosimeter project.
Harold Javitz
Harold Javitz received his PhD in Statistics from the University of California at Berkeley. He is a senior statistician at SRI International. His research interests include smoking cessation, biostatistics and educational studies.
Susan J. Knox
Susan Knox received her Ph.D. in Microbiology from UC Davis and her MD from Stanford University. She did residency and fellowship training at Stanford and has been on the faculty there in Radiation Oncology since 1990.
Shirley Lee
Shirley Lee received her MS in Computer Science from Indiana University and has worked at SRI since 2011 in the area of bioinformatics and computational and statistical analysis methods with emphasis on classification and dynamic automation.
Hua Lin
Hua Lin received her PhD in Chemistry from Fudan University (China) in 1989. She joined SRI in 2010 and is specialized for biomarker development. Her research interests are focused on proteomics and methodologies for ultra-sensitive sample analysis.
Thomas Shaler
Thomas Shaler received his Ph.D. in Organic Chemistry from the University of California. His work at SRI International currently centers on the development of mass spectrometric analysis techniques for biological, biomedical and biotechnology applications.
Lei Shura
Lei Shura received her MS in Neurosciences from Kent State University in 1998. She worked at Stanford University for 2 years as a Life Science Researcher and 6 years as a Clinical Research Coordinator. She managed multiple clinical studies with various phases in Radiation Oncology from start-up to close-out.
Paul Stein
Paul Stein received his PhD in Cell and Developmental Biology from State University of New York, Stony Brook. He joined SRI International in 2010. His research interests focus on signaling pathways in inflammation and autoimmunity. He also directs immunoassay development to support various biomarker programs.
Kathryn Todd
Kathryn Todd received her PhD in Physics from Stanford University in 2009 and has worked at SRI since 2010 as a research engineer, program manager, and associate laboratory director. Her research and development interests include Point of Care In Vitro Diagnostics, nanopore-based molecular diagnostics, and two-dimensional materials.
David E. Cooper
David E. Cooper received his PhD in Physics from MIT in 1980 and has worked in the area of medical devices, biosensors, and molecular diagnostics since 1996. Dr. Cooper served as the PI for this work.