Center for High-Throughput Minimally-Invasive Radiation Biodosimetry

摘要/摘要 这一行政补充申请是对已获批准的母公司CMCRC的改进 GRANT(U19 AI067773)，范围不变。它的动机是a)意外的成本增加 用于招募儿童献血者到该项目由于新冠肺炎，和b)一个新的可用的(自父母 批准提交/批准)通过新的超高剂量率大幅提高辐射剂量率能力 与IND的即时辐射闪光的极高剂量率相匹配的技术。两者都有 这些拟议的增额属于核定赔偿金的范围。具体地说，原始的 儿科病人招募计划以利用当地儿科诊所招募儿童为中心， 参加每年一度的探井。在新冠肺炎大流行的背景下，这种做法已经成为 这是站不住脚的，因为目前参加这些探井的孩子更少了，而探井的那些父母 接受采访的人远不像以前那样愿意让他们的孩子入学。要克服这一点， 已经与JB临床研究(JBR)建立了合作伙伴关系，我们之前曾与JBR合作 一项由BARDA赞助的大型人口统计研究。JBR有一份活跃的潜在献血者名单， 包括儿科，并能够从他们的数据库中主动招募捐赠者，并为我们提供血液 这项研究的样本。首要目标仍然是了解不同的剂量率是否/如何调制 我们已经开发的预测生物标记物的响应，特别是为了解决关于 儿童样本对高剂量率与低剂量率的反应是否与成人不同。在高剂量下 速率结束，剂量率效应特别重要，因为来自IND的即时辐射通常 在几微秒内就送到了。相比之下，大多数实验室辐照器的剂量率约为1 因此不能模拟这些高剂量率照射。在最初的提案中，我们有 建议比较标准剂量率(~1GY/分钟)和较高剂量率(3-10GY/秒)-后者 使用标准的临床直线加速器提供。然而，这一较高的剂量率仍然远远低于 IND发出的即时辐射的剂量率(&gt；105Gy/S)。因为父母的拨款是 提交和资助，我们已经开发了一种新型的超高剂量率辐照器，基于退役的 瓦里安·克林克直线加速器。通过将待照射的样品放在极高的Clinac头部内 提供剂量率；例如，3Gy剂量可以在10微秒的S(微秒)内传递，即一次剂量 辐射剂量率约为300,000 GY/秒--与IND的即时辐射剂量率相当。因此 在本补编中，建议将儿科人口学研究从三个剂量率(低 4种剂量率(低剂量率vs.1 Gy/min vs.3-10Gy/秒vs.3-10Gy/秒)。 3Gy10微米S)。

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).