Center for High-Throughput Minimally-Invasive Radiation Biodosimetry

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SUMMARY / ABSTRACT This request for an Administrative Supplement represents an enhancement of the approved parent CMCRC grant (U19 AI067773) without any change in its scope. It is motivated by a) an unanticipated increase in costs for recruiting pediatric blood donors to the project due to COVID-19, and b) a newly available (since the parent grant submittal / approval) major increase in radiation dose rate capabilities through a new ultra high dose rate technology which matches the extremely high dose rates from the prompt radiation flash from an IND. Both these proposed augmentations fall within the scope of the approved award. Specifically, the original recruitment plan for pediatric patients centered around utilizing local pediatric clinics to recruit children, attending annual well-visits. Within the context of the COVID-19 pandemic, this approach has become untenable as far fewer children are currently attending these well-visits, and those parents at the well visits that have been interviewed are far less willing than before to have their children enrolled. To overcome this a partnership has been established with JB Clinical Research (JBR), whom we have previously collaborated with on a large demographic study sponsored by BARDA. JBR have an active list of potential blood donors, including pediatrics, and are able to proactively recruit donors from their database and provide us with blood samples for this study. The overarching goal remains to understand if / how different dose rates modulate the response of the predictive biomarkers that we have developed and in particular to address the question as to whether pediatric samples have a different response to high vs. low dose rates than adults. At the high dose rate end, dose rate effects are particularly important in that the prompt radiation from an IND will typically be delivered in a few microseconds. By contrast, most laboratory irradiators give dose rates of approximately 1 Gy/min, and thus cannot simulate these high dose rate exposures. Within the original proposal we had proposed comparing standard dose rates (~1 Gy/ min) with higher dose rates (3-10 Gy/sec) – the latter delivered using a standard clinical linear accelerator. However, this higher dose rate is still far less than the dose rate at which the prompt radiation from an IND is delivered (>105 Gy/s). Since the parent grant was submitted and funded, we have developed a novel ultra high dose rate irradiator, based on a decommissioned Varian Clinac linear accelerator. By placing the sample to be irradiated within the Clinac head, extremely high dose rates are available; for example, a 3 Gy dose can be delivered in 10 µs (microseconds), i.e. at a dose rate of ~300,000 Gy/sec - which is comparable to the prompt radiation dose rate from an IND. Consequently within this supplement it is proposed to expand the pediatric demographic study from three dose rates (low dose rate vs.1 Gy/min vs. 3-10 Gy/sec) to four dose rates (low dose rate vs.1 Gy/min vs. 3-10 Gy/sec vs. 3 Gy / 10 µs).