Explaining Biodosimetry
What is biodosimetry?
- Use of clinical and laboratory observations to estimate radiation dose received after exposure or internal contamination
- Biodosimetry typically does not measure radioactivity directly.
- Biodosimetry measures a clinical or laboratory surrogate endpoint and correlates it with a radiation dose estimated to have produced that effect.
- The REMM Dose Estimator includes 3 methods of calculating dose
- Time to vomiting post-exposure
- Lymphocyte depletion kinetics
- Dicentric chromosomes assay
- New tools1 with faster throughput and better accuracy for acute dosimetry are under development.
- Other tools2 are used for estimating dose long after the event has occurred.
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What is the difference between biodosimetry and bioassay?
- Biodosimetry is defined above.
- Bioassay is used to test whether and how much internal radiation contamination has occurred by measuring radioactivity directly in biological specimens like blood, urine, feces, sweat or other materials.
- Bioassay results can be used to
- Distinguish those who were or were not internally contaminated
- Estimate how much contamination occurred
- Calculate radiation dose to the whole body or to a specific organ.
- Measure the effectiveness over time of treatments for internal contamination
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Why is knowing radiation dose information clinically useful?
- Acute Radiation Syndrome (ARS) severity depends on
- Dose related factors
- Host factors
- Examples include extremes of age, extremes of health, diminished immune function
- Whether the victim received trauma as well as radiation (combined injury)
- The greater the whole body radiation dose
- The earlier the onset of signs and symptoms of ARS.
- The more severe the clinical manifestations
- The worse the clinical outcome
- Knowing the whole body radiation dose facilitates
- Selection of appropriate prophylactic and therapeutic measures
- Estimation of prognosis, which is especially useful in mass casualty situations when resources may be limited
- Transfer of appropriate patients to facilities with the expertise to manage severe ARS
- Although most therapy for ARS is directed at actual clinical signs and symptoms, clinical effects of ARS can be anticipated and potentially mitigated based biodosimetry, as with the use of prophylactic white cell cytokines.
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What is dose reconstruction?
- Knowing a victim's location in relation to the epicenter of a radiation event, when they were there, and for how long, can provide an estimate of a whole body radiation dose, after the plume maps have been constructed.
(See Time, Distance, Shielding Illustration)
(See Dose Reconstruction)
(See Plume Maps)
- Time: How long did the patient spend in the radiation field? The longer an individual spends in a radiation field, the greater the overall whole-body radiation dose.
- Distance: Where was the patient located relative to the epicenter of the radiation event? Radiation plume maps of the event will show the radiation levels within the impacted geographical area. Sequential maps will show how the radiation levels change over time at various distances from the epicenter.
- Shielding: Was the patient protected by any significant shielding, (e.g building walls of wood vs. concrete) that could have attenuated their whole body radiation dose?
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What clinical clues provide estimates of dose? 3
- Evaluate subsyndrome severity scores for the 4 ARS subsyndromes
- A higher severity score for any of the subsyndromes is generally correlated with higher exposure dose
- Subsyndromes
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What should you do when there are conflicting dose estimates? 4
- Use the highest whole body dose estimate to plan treatment initially.
- Modify the estimate and treatment as more accurate information becomes available.
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- Acute event triage and management
- The dicentric chromosome assay is the current "gold standard" for biodosimetry although results may not be available for days to weeks, especially in a mass casualty event.
- To facilitate more rapid analysis, as few as 20 metaphases may be scored to provide a preliminary estimate of dose, although scoring 50 probably provides a more accurate result. Scoring should be increased to 50 cells where there is disagreement with the initial assessments or evidence of significantly inhomogeneous exposure.
- Dose-related effects of radiation are seen if blood for chromosomal analysis is drawn at least 24 hours after exposure, but useful information can probably be obtained if the blood is drawn within a few weeks.
- Victims with a potential whole body dose in the range of 1.5-3 Gy
- May be at risk for the ARS hematological subsyndrome and lymphocyte depletion kinetics may not be as accurate as the dicentric assay in estimating dose in this range, especially if radiation exposure occurred over a few days.
- May develop cytopenias 21-28 days after exposure and they should be triaged to a medical facility with expertise in radiation medicine. The assay may help evaluate these patients.
- Victims with a potential whole body dose higher than 1-3 Gy
- May become symptomatic and pancytopenic before the results of the dicentric assay become available. Nevertheless, dicentric assay results will provide useful confirmatory information
- Risk assessment for carcinogenicity
- Although there are currently no known effective interventions to prevent cancer, an exposure-based risk assessment may be useful in directing follow-up.
- If a victim's dose from exposure is estimated to have been <0.25 Gy, he/she will have a very low additional lifetime risk of cancer from radiation exposure. Special follow-up based on radiation exposure is not recommended for these individuals.
- Victims whose dicentric assay suggests a whole body dose between 0.25-1 Gy are unlikely to develop significant ARS, but have a low (but measurable) risk for radiation-induced cancer5. Such individuals require long term follow-up.
- The dicentric assay may be useful for evaluating the large number of individuals in a mass casualty event who were not ill but who received some exposure, perhaps > 1 Gy. Results can provide information about potential future risk and help generate guidance about monitoring and follow-up5.
- See REMM information about the Estimate of Lifetime Excess Risk of Fatal Cancer Due to Short-term Radiation
- See REMM information about the Health Risks from Exposure to Low Levels of Ionizing Radiation
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- Lymphocyte depletion kinetics will be the primary source of biodosimetry information initially, because CBCs will be available more easily and rapidly, especially after a mass casualty event.
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References |
- Alexander, G.A., et al., BiodosEPR-2006 Meeting: Acute dosimetry consensus committee recommendations on biodosimetry applications in events involving uses of radiation by terrorists and radiation accidents. Radiat. Meas. (2007), doi: 10.1016/j.radmeas.2007.05.035 (PDF - 518 KB) (In Press)
- Radiation Dosimetry Monograph: "Applications of Dosimetry in Radiation Epidemiology" (Radiation Research, July 2006, Volume 166, Number 1. Special Supplement) (HHS/National Cancer Institute/Division of Cancer Epidemiology and Genetics)
- Fliedner TM, Friesecke I, Beyrer K. Medical Management of Radiation Accidents: Manual on the Acute Radiation Syndrome. Oxford: British Institute of Radiology, 2001.
- Lloyd DC; Edwards AA; Moquet JE; Guerrero-Carbajal YC. The role of cytogenetics in early triage of radiation casualties. Appl Radiat Isot 2000 May;52(5):1107-12. [PubMed Citation]
- Introduction to radiation physics and dosimetry (PDF -4.67 MB) (Steven L. Simon, Radiation Epidemiology Course, May 2007, HHS/National Cancer Institute/Division of Cancer Epidemiology and Genetics)
- Waselenko JK, MacVittie TJ, Blakely WF, Pesik N, Wiley AL, Dickerson WE, Tsu H, Confer DL, Coleman CN, Seed T, Lowry P, Armitage JO, Dainiak N; Strategic National Stockpile Radiation Working Group. Medical management of the acute radiation syndrome: recommendations of the Strategic National Stockpile Radiation Working Group. Ann Intern Med. 2004 Jun 15;140(12):1037-51. [PubMed Citation]
- Acute Radiation Syndrome: A Fact Sheet for Physicians (HHS/CDC)
- Waselenko JK, Armitage JO, Dainiak N. Treatment of radiation injury in the adult. www.UpToDate.com (Subscription required)
- Waselenko JK, Dainiak N. Biology and clinical features of radiation injury in adults. www.UpToDate.com (Subscription required)
- See Dose Estimators (Biodosimetry Tools) for more references on dicentrics and other biodosimetry assays
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