Physically-based biodosimetry using in vivo EPR of teeth in patients undergoing total body irradiation

Purpose: The ability to estimate individual exposures to radiation following a large attack or incident has been identified as a necessity for rational and effective emergency medical response. In vivo electron paramagnetic resonance (EPR) spectroscopy of tooth enamel has been developed to meet this need. Materials and methods: A novel transportable EPR spectrometer, developed to facilitate tooth dosimetry in an emergency response setting, was used to measure upper incisors in a model system, in unirradiated subjects, and in patients who had received total body doses of 2 Gy. Results: A linear dose response was observed in the model system. A statistically significant increase in the intensity of the radiation-induced EPR signal was observed in irradiated versus unirradiated subjects, with an estimated standard error of dose prediction of 0.9 ± 0.3 Gy. Conclusions: These results demonstrate the current ability of in vivo EPR tooth dosimetry to distinguish between subjects who have not been irradiated and those who have received exposures that place them at risk for acute radiation syndrome. Procedural and technical developments to further increase the precision of dose estimation and ensure reliable operation in the emergency setting are underway. With these developments EPR tooth dosimetry is likely to be a valuable resource for triage following potential radiation exposure of a large population.

[1]  Benjamin B Williams,et al.  SURFACE LOOP RESONATOR DESIGN FOR IN VIVO EPR TOOTH DOSIMETRY USING FINITE ELEMENT ANALYSIS , 2010, Health physics.

[2]  David C Lloyd,et al.  WHO 1st Consultation on the Development of a Global Biodosimetry Laboratories Network for Radiation Emergencies (BioDoseNet) , 2009, Radiation research.

[3]  J. Buckey,et al.  EPR spectrometer for clinical applications , 2005, Magnetic resonance in medicine.

[4]  P. Starewicz,et al.  Measurements of clinically significant doses of ionizing radiation using non-invasive in vivo EPR spectroscopy of teeth in situ. , 2005, Applied radiation and isotopes : including data, instrumentation and methods for use in agriculture, industry and medicine.

[5]  V. Chumak,et al.  Some aspects of EPR dosimetry of liquidators. , 2000, Applied radiation and isotopes : including data, instrumentation and methods for use in agriculture, industry and medicine.

[6]  B. Halligan,et al.  THE URINE PROTEOME FOR RADIATION BIODOSIMETRY: EFFECT OF TOTAL BODY VS. LOCAL KIDNEY IRRADIATION , 2010, Health physics.

[7]  H. Swartz,et al.  Experimental Procedures for Sensitive and Reproducible In Situ EPR Tooth Dosimetry. , 2007, Radiation measurements.

[8]  Irena Nowak,et al.  VALIDATING HIGH-THROUGHPUT MICRONUCLEUS ANALYSIS OF PERIPHERAL RETICULOCYTES FOR RADIATION BIODOSIMETRY: BENCHMARK AGAINST DICENTRIC AND CBMN ASSAYS IN A MOUSE MODEL , 2010, Health physics.

[9]  M. Bittner,et al.  Differential responses of stress genes to low dose-rate gamma irradiation. , 2003, Molecular cancer research : MCR.

[10]  M. Sasaki,et al.  Advances in the biophysical and molecular bases of radiation cytogenetics , 2009, International journal of radiation biology.

[11]  H. Swartz,et al.  Differentiation of the observed low frequency (1200MHz) EPR signals in whole human teeth. , 2005, Applied radiation and isotopes : including data, instrumentation and methods for use in agriculture, industry and medicine.

[12]  W. Blakely,et al.  COMBINED APPROACH OF HEMATOLOGICAL BIOMARKERS AND PLASMA PROTEIN SAA FOR IMPROVEMENT OF RADIATION DOSE ASSESSMENT TRIAGE IN BIODOSIMETRY APPLICATIONS , 2010, Health physics.

[13]  D. Schauer,et al.  Electron paramagnetic resonance (EPR) biodosimetry , 2001 .

[14]  R. J. Nicolalde,et al.  Implementing EPR Dosimetry for Life-Threatening Incidents: Factors Beyond Technical Performance. , 2007, Radiation measurements.

[15]  N. Draper,et al.  Applied Regression Analysis. , 1967 .

[16]  R. J. Nicolalde,et al.  In Vivo EPR For Dosimetry. , 2007, Radiation measurements.

[17]  Richard A Britten,et al.  THE IDENTIFICATION OF SERUM BIOMARKERS OF HIGH-LET RADIATION EXPOSURE AND BIOLOGICAL SEQUELAE , 2010, Health physics.

[18]  J. Armitage,et al.  Medical Management of the Acute Radiation Syndrome: Recommendations of the Strategic National Stockpile Radiation Working Group , 2004, Annals of Internal Medicine.

[19]  V. Stepanenko,et al.  Wide scale EPR retrospective dosimetry. Results and problems , 1997 .

[20]  N. Nakamura,et al.  Contamination from possible solar light exposures in ESR dosimetry using human tooth enamel. , 1998, Journal of radiation research.

[21]  J. Puskar,et al.  Paramagnetic resonance in tooth enamel created by ultraviolet light. , 1996, Applied radiation and isotopes : including data, instrumentation and methods for use in agriculture, industry and medicine.

[22]  Harold M. Swartz,et al.  BiodosEPR-2006 Meeting: Acute dosimetry consensus committee recommendations on biodosimetry applications in events involving uses of radiation by terrorists and radiation accidents , 2007 .

[23]  R. J. Nicolalde,et al.  A CRITICAL ASSESSMENT OF BIODOSIMETRY METHODS FOR LARGE-SCALE INCIDENTS , 2010, Health physics.

[24]  M. B. Grace,et al.  Human In vivo Radiation-Induced Biomarkers , 2004, Cancer Research.

[25]  H. Swartz,et al.  Electronically tunable surface-coil-type resonator for L-band EPR spectroscopy. , 2000, Journal of magnetic resonance.

[26]  P. Starewicz,et al.  In vivo EPR dosimetry to quantify exposures to clinically significant doses of ionising radiation. , 2006, Radiation protection dosimetry.

[27]  R. Goans,et al.  Early dose assessment in criticality accidents. , 2001, Health physics.

[28]  Michael Fenech,et al.  THE LYMPHOCYTE CYTOKINESIS-BLOCK MICRONUCLEUS CYTOME ASSAY AND ITS APPLICATION IN RADIATION BIODOSIMETRY , 2010, Health physics.

[29]  E. Lund,et al.  The effects of UV-irradiation on the ESR-dosimetry of tooth enamel. , 2001, Applied radiation and isotopes : including data, instrumentation and methods for use in agriculture, industry and medicine.

[30]  R. J. Nicolalde,et al.  THE VIEW FROM THE TRENCHES: PART 2–TECHNICAL CONSIDERATIONS FOR EPR SCREENING , 2010, Health physics.

[31]  P. Zhou,et al.  Dose-dependent expression changes of early response genes to ionizing radiation in human lymphoblastoid cells. , 2007, International journal of molecular medicine.

[32]  Ralf Lenigk,et al.  BIODOSIMETRY ON SMALL BLOOD VOLUME USING GENE EXPRESSION ASSAY , 2010, Health physics.

[33]  Abel J. González,et al.  An international perspective on radiological threats and the need for retrospective biological dosimetry of acute radiation overexposures , 2007 .

[34]  Paola Fattibene,et al.  EPR dosimetry with tooth enamel: A review. , 2010, Applied radiation and isotopes : including data, instrumentation and methods for use in agriculture, industry and medicine.

[35]  O. Hyrien,et al.  DYNAMICS OF MICRONUCLEI IN MOUSE SKIN FIBROBLASTS AFTER GAMMA IRRADIATION , 2010, Health physics.

[36]  A. Bouville,et al.  UV EFFECTS IN TOOTH ENAMEL AND THEIR POSSIBLE APPLICATION IN EPR DOSIMETRY WITH FRONT TEETH , 2010, Health physics.

[37]  E. Demidenko,et al.  Radiation dose reconstruction from L-band in vivo EPR spectroscopy of intact teeth: Comparison of methods. , 2007, Radiation measurements.

[38]  N. Draper,et al.  Applied Regression Analysis: Draper/Applied Regression Analysis , 1998 .

[39]  Brian R. Moyer,et al.  RAPID RADIATION DOSE ASSESSMENT FOR RADIOLOGICAL PUBLIC HEALTH EMERGENCIES: ROLES OF NIAID and BARDA , 2010, Health physics.

[40]  Jian Zhang,et al.  THE RABIT: A RAPID AUTOMATED BIODOSIMETRY TOOL FOR RADIOLOGICAL TRIAGE , 2010, Health physics.

[41]  R. Wilkins,et al.  QUICKSCAN DICENTRIC CHROMOSOME ANALYSIS FOR RADIATION BIODOSIMETRY , 2010, Health physics.

[42]  J. S. Hyde,et al.  Chapter 2 Electron spin resonance , 1985 .

[43]  J. Buckey,et al.  Clinical applications of EPR: overview and perspectives , 2004, NMR in biomedicine.

[44]  M. Bittner,et al.  Differential Responses of Stress Genes to Low Dose-Rate ; Irradiation , 2003 .

[45]  James Armitage,et al.  Medical Management of the Acute Radiation Syndrome: Recommendations of the Strategic National Stockpile Radiation Working Group , 2004, Annals of Internal Medicine.

[46]  Harold M Swartz,et al.  In vivo measurements of EPR signals in whole human teeth. , 2005, Applied radiation and isotopes : including data, instrumentation and methods for use in agriculture, industry and medicine.

[47]  Hiroshi Hirata,et al.  An improved external loop resonator for in vivo L-band EPR spectroscopy. , 2003, Journal of magnetic resonance.

[48]  R C Ricks,et al.  Early dose assessment following severe radiation accidents. , 1997, Health physics.

[49]  R. J. Nicolalde,et al.  DEVELOPMENT OF IN VIVO TOOTH EPR FOR INDIVIDUAL RADIATION DOSE ESTIMATION AND SCREENING , 2010, Health physics.

[50]  Harold M. Swartz,et al.  L-band electron paramagnetic resonance spectrometer for use in vivo and in studies of aqueous biological samples , 2005 .