The re-activatable Yb-169 radiation source: a therapeutic medical device to reduce the risk of brachytherapy and increase adoption

项目摘要/摘要： 目前，高剂量率近距离放射治疗(HDR-BT)存在技术空白，阻碍了疗效 单组分HDR-BT单一疗法用于前列腺癌患者，并正在防止从侵袭性转向 宫颈癌患者的间质内近距离放射治疗改为仅腔内放射治疗。造成差距的原因是 HDR-BT的辐射剂量整合限制，在找到解决方案之前，前列腺癌HDR-BT将 由于几何限制，继续存在剂量一致性限制，需要多个针头植入 和/或住院治疗，宫颈癌的治疗将继续是侵入性的、具有挑战性的和时间紧迫的- 苏明，病人探视有限。长期目标是转移一种名为ReNeu的技术，用于发电 169 Yb源，可显著提高辐射剂量一致性，并使用商业模式进入临床使用 基于通过在核反应堆中重新激活而实现的大量成本节约。总体目标 这个项目的目的是展示ReNeu的技术优势、可行性和商业潜力，这是 预计将使旋转屏蔽式近距离放射治疗(RSBT)方法能够改善剂量一致性。169Yb是 RSBT的理想同位素，因为它的比活度足够高，足以与传统的~(192)Ir剂量率相匹配。 相似的源体积，发射的伽马射线能量足够低，可以部分屏蔽。建议数 使169Yb在商业上可行的方法是简单地将源体积从1mm3增加到3mm3， 同时保持传统的源直径。信号源最多可以(重新)激活11次，并且， 在前期工作的基础上，这一过程可以将169Yb源每临床年的总成本降低75%。 这项工作的基本原理是，ReNeu将提供使RSBT在商业上可行的框架， 实现近距离放射治疗的改进，每年可使数万名患者受益。一次演示 ReNeu方法的可行性将通过实现两个具体目标来解决：(1)开发一种机械-- 临床原型ReNeu源/线，可用于临床；(2)开发ReNeu的(重新)激活模型 以验证其临床和商业潜力。在目标1下，将建造一个169Yb源，其体积为3mm3 音量，连同它的控制导丝，将能够重新激活。人们的预期是， 信号源/电线将成功通过FDA批准所需的测试。在AIM 2下，169Yb(重新)激活 基于初步数据的模型将经过实验校准，将适用于最多11次(重新)激活。 预计每次(重新)激活将平均需要9天，具有平均临床来源生命周期 在41天的每次(重新)激活后。这一贡献预计将是重大的，因为它消除了一个主要的 阻碍改进可使前列腺癌和宫颈癌患者受益的近距离放射治疗。这项工作是 创新是因为ReNeu源的体积增加了3mm3，与低曲率RSBT相结合 应用程序代表着与现状的实质性偏离，因为它独特地提供了以下能力： 有效地提供单次前列腺癌治疗和非侵入性治疗宫颈癌。

PROJECT SUMMARY/ABSTRACT: There is currently a technological gap in high-dose-rate brachytherapy (HDR-BT) that has stunted the efficacy of single-fraction HDR-BT monotherapy for prostate cancer patients and is preventing a shift away from invasive interstitial brachytherapy to an intracavitary-only approach for cervical cancer patients. The gap is due to the radiation dose conformity limitations of HDR-BT, and, until a solution is developed, prostate cancer HDR-BT will continue to have dose conformity limitations due to geometric constraints, requiring multiple needle implants and/or a hospital stay, and cervical cancer treatments will continue to be invasive, challenging, and time-con- suming, with limited patient access. The long-term goal is to transfer a technology, called ReNeu, for generating 169Yb sources that can dramatically improve radiation dose conformity, into clinical usage using a business model based on the substantial cost savings achieved through re-activation in a nuclear reactor. The overall objective of this project is to demonstrate the technical merit, feasibility, and commercial potential of ReNeu, which is expected to enable the rotating shield brachytherapy (RSBT) approach to improving dose conformity. 169Yb is an ideal isotope for RSBT since its specific activity is high enough to match the dose rate of conventional 192Ir in a similar source volume, and the emitted gamma ray energy is low enough for partial shielding. The proposed approach for making 169Yb commercially feasible is to simply increase source volume from 1 mm3 to 3 mm3, while maintaining the conventional source diameter. The source could be (re)activated up to 11 times, and, based on preliminary work, this process could reduce the overall cost per clinic-year of 169Yb sources by 75%. The rationale for this work is that ReNeu will provide the framework that will make RSBT commercially viable, enabling brachytherapy improvements that could benefit tens of thousands of patients per year. A demonstration of feasibility for the ReNeu approach will be addressed by carrying out two specific aims: (1) Develop a mechan- ical prototype ReNeu source/wire that enables clinical usage and (2) Develop the (re)activation model for ReNeu to validate its clinical and commercial potential. Under aim 1, a 169Yb source will be constructed with a 3 mm3 volume that, along with its controlling guidewire, will be capable of re-activation. The expectation is that the source/wire will successfully pass the tests needed for FDA clearance. Under aim 2, the 169Yb (re)activation model based on preliminary data will be experimentally calibrated, which will apply for up to 11 (re)activations. The expectation is that each (re)activation will take 9 days on average, with an average clinical source lifetime after each (re)activation of 41 days. This contribution is expected to be significant because it removes a major impediment to improving brachytherapy that could benefit prostate and cervical cancer patients. This work is innovative because the ReNeu source's increased volume of 3 mm3 in combination with low-curvature RSBT applicators represents a substantive departure from the status quo by uniquely providing the capability to cost- effectively deliver single-fraction prostate cancer treatments and non-invasively treat cervical cancer.