Abstract
In order to address mass casualty situations in the event of radiation exposure from nuclear attacks or accidents, there is an urgent and unmet need for point-of-care (POC) diagnostic devices for rapid assessment of absorbed radiation dose. Patients receiving whole body irradiation (WBI), which is often included as part of the preparative regimen prior to hematopoietic stem cell transplantation (HSCT), can be used as subjects for evaluation of radiation biodosimeters that may be of use in a nuclear event as well as in radiation therapy. The level of WBI exposure in patients is frequently associated with treatment-related complications to multiple tissues and involves individual variations in radiosensitivity. Thus, early and predictive indicators of individual outcomes of radiation exposure would allow pre-emptive clinical management before the onset of tissue injury. To address these critical needs, we are developing an ocular dosimeter (OCDOS) that noninvasively assesses radiation-induced damage by measuring light scattered by proteins present in the aqueous humor (AH) the eye. Therefore, we initiated a clinical study to assess the potential of OCDOS in patients before and during a fractionated course of WBI conditioning therapy prior to HSCT. Early results in three patients show a clear difference in light scattering properties of the AH from measurements taken before and after irradiation that persists for several days into treatment. This preliminary study provides proof of principle that this non-invasive and POC device can assess dose-related changes in proteins in patients receiving WBI and is suitable for high throughput, triage assessment of individuals exposed in a mass casualty scenario of a nuclear event.
Highlights
Current biodosimetric approaches for estimating radiation dose and anticipating the effects of exposure from nuclear events often require tissue collection, sampling and laboratory-intensive methodologies with results typically not available for several days [1]
The ocular dosimeter (OCDOS) instrument was calibrated using an in vitro eye model (Figure 3). This was performed by measuring the response of the OCDOS system to varying proportions of the two most abundant proteins in the AH: albumin (69kDa) and immunoglobulin G (IgG) (150kDa) at equal concentrations (0.2mg/ml) in a synthetic aqueous humor buffer solution [8]
It demonstrates that OCDOS can distinguish significant light-scattering changes in the AH attributed to an increase in protein concentration and/or average protein molecular weight and radius, even after the first dose of 1.5 or 1.65 Gy
Summary
Current biodosimetric approaches for estimating radiation dose and anticipating the effects of exposure from nuclear events often require tissue collection, sampling and laboratory-intensive methodologies with results typically not available for several days [1]. It is well-recognized that there is a wide inter-patient variation in normal tissue reactions to radiotherapy and identifying patients likely to develop severe reactions would be a considerable advance by allowing dose to be individually tailored [2,3,4]. These patients are useful for testing POC radiation biodosimeters that might be of use in the clinic and for rapid triage after nuclear events in allocating subjects for appropriate treatment with potential mitigating therapies [1, 6]
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