title: Rapid and High-Throughput Detection and Quantitation of Radiation Biomarkers in Human and Nonhuman Primates by Differential Mobility Spectrometry-Mass Spectrometry.
abstract: Radiation exposure is an important public health issue due to a range of accidental and intentional threats. Prompt and effective large-scale screening and appropriate use of medical countermeasures (MCM) to mitigate radiation injury requires rapid methods for determining the radiation dose. In a number of studies, metabolomics has identified small-molecule biomarkers responding to the radiation dose. Differential mobility spectrometry-mass spectrometry (DMS-MS) has been used for similar compounds for high-throughput small-molecule detection and quantitation. In this study, we show that DMS-MS can detect and quantify two radiation biomarkers, trimethyl-L-lysine (TML) and hypoxanthine. Hypoxanthine is a human and nonhuman primate (NHP) radiation biomarker and metabolic intermediate, whereas TML is a radiation biomarker in humans but not in NHP, which is involved in carnitine synthesis. They have been analyzed by DMS-MS from urine samples after a simple strong cation exchange-solid phase extraction (SCX-SPE). The dramatic suppression of background and chemical noise provided by DMS-MS results in an approximately 10-fold reduction in time, including sample pretreatment time, compared with liquid chromatography-mass spectrometry (LC-MS). DMS-MS quantitation accuracy has been verified by validation testing for each biomarker. Human samples are not yet available, but for hypoxanthine, selected NHP urine samples (pre- and 7-d-post 10 Gy exposure) were analyzed, resulting in a mean change in concentration essentially identical to that obtained by LC-MS (fold-change 2.76 versus 2.59). These results confirm the potential of DMS-MS for field or clinical first-level rapid screening for radiation exposure. Graphical Abstract ᅟ.
authors.affiliation: Department of Chemistry and Chemical Biology, Northeastern University, Boston, MA, 02115, USA.
authors.forename: Zhidan
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Chemistry and Chemical Biology, Northeastern University, Boston, MA, 02115, USA. steve.coy@post.harvard.edu.
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Coy
authors.affiliation: Department of Biochemistry and Molecular and Cellular Biology, Georgetown University Medical Center, Washington, DC, 20057, USA.
authors.forename: Evan L
authors.initials: EL
authors.lastname: Pannkuk
authors.affiliation: Department of Biochemistry and Molecular and Cellular Biology, Georgetown University Medical Center, Washington, DC, 20057, USA.
authors.forename: Evagelia C
authors.initials: EC
authors.lastname: Laiakis
authors.affiliation: Department of Chemistry and Chemical Biology, Northeastern University, Boston, MA, 02115, USA.
authors.forename: Adam B
authors.initials: AB
authors.lastname: Hall
authors.affiliation: Department of Biochemistry and Molecular and Cellular Biology, Georgetown University Medical Center, Washington, DC, 20057, USA.|Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, 20057, USA.|Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, 22254, Saudi Arabia.
authors.forename: Albert J
authors.initials: AJ
authors.lastname: Fornace
authors.affiliation: Department of Chemistry and Chemical Biology, Northeastern University, Boston, MA, 02115, USA. p.vouros@neu.edu.|Barnett Institute of Chemical and Biological Analysis, Northeastern University, Boston, MA, 02115, USA. p.vouros@neu.edu.
authors.forename: Paul
authors.initials: P
authors.lastname: Vouros
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000032:analysis*; D002853:Chromatography, Liquid; D006801:Humans; D011323:Primates; D000069079:Radiation Exposure / Q000032:analysis*; D013057:Spectrum Analysis; D053719:Tandem Mass Spectrometry
chemical_list: D015415:Biomarkers
keywords: Biomarkers; DMS-MS; Differential mobility spectrometry; FAIMS-MS; Field asymmetric waveform ion mobility spectrometry; Gamma radiation; Human; Nonhuman primates; Radiation exposure