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

可重新激活的 Yb-169 放射源：一种治疗医疗设备，可降低近距离放射治疗的风险并提高采用率

• 批准号: 10383611
• 负责人: RYAN Thomas FLYNN
• 金额: $ 30万
• 依托单位: PXALPHA, LLC
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-01 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10383611
• 关键词: Address; Adoption; Ambulatory Care; Biochemical; Brachytherapy; Businesses; Caliber; Cancer Patient; Clinic; Clinical; Clinical Trials; Collaborations; Consumption; Cost Savings; Data; Development; Devices; Diagnosis; Dose; Dose-Rate; Foundations; Funding; Gamma Rays; Goals; Gold; High-Dose Rate Brachytherapy; Implant; Iowa; Isotopes; Length of Stay; Letters; Malignant neoplasm of cervix uteri; Malignant neoplasm of prostate; Mechanics; Medical Device; Mission; Modeling; Needles; Neutrons; Nuclear Reactors; Operative Surgical Procedures; Organ; Patients; Phase; Photons; Physicians; Price; Procedures; Process; Prostate; Prostate Cancer therapy; Prostatic Urethra; Provider; Public Health; Radiation; Radiation Dose Unit; Research; Residual state; Risk; Site; Small Business Technology Transfer Research; Source; Sum; Technology; Testing; Therapeutic; Time; Toxic effect; United States National Institutes of Health; Universities; Urethra; Validation; Work; base; cancer therapy; clinically relevant; commercialization; cost; cost effective; expectation; improved; in silico; innovation; interstitial; irradiation; novel; prevent; programs; prototype; success; tumor

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.

项目总结/摘要： 目前高剂量率近距离放射治疗（HDR-BT）存在技术差距， 单次HDR-BT单药治疗前列腺癌患者，并防止从侵入性 间质性近距离放射治疗到宫颈癌患者的仅腔内方法。差距是由于 HDR-BT的辐射剂量符合性限制，并且，直到开发出解决方案，前列腺癌HDR-BT将 由于几何约束，需要多次针植入，继续存在剂量符合性限制 和/或住院，宫颈癌治疗将继续是侵入性的，具有挑战性的，时间上的， 患者访问受限。长期目标是转让一种名为ReNeu的技术， 169 Yb源，可以显着提高辐射剂量一致性，进入临床使用的商业模式 基于通过在核反应堆中重新激活实现的大量成本节省。总体目标 该项目的目的是展示ReNeu的技术优势、可行性和商业潜力， 预计将使旋转屏蔽近距离放射治疗（RSBT）的方法，以提高剂量符合性。169 Yb 这是RSBT的理想同位素，因为它的比活度足够高，可以与常规192 Ir的剂量率相匹配， 类似的源体积，并且发射的伽马射线能量足够低以用于部分屏蔽。拟议 制造169 Yb商业上可行的方法是简单地将源体积从1 mm 3增加到3 mm 3， 同时保持传统的源直径。该源可以被（重新）激活多达11次，并且， 基于初步工作，该过程可以将169 Yb源的每个临床年的总成本降低75%。 这项工作的基本原理是，ReNeu将提供一个框架，使RSBT在商业上可行， 使近距离放射治疗的改进能够每年使成千上万的患者受益。示范 ReNeu方法的可行性将通过实现两个具体目标来解决：（1）开发一种机制， 支持临床使用的标准原型ReNeu源/导丝，以及（2）开发ReNeu的（再）激活模型 以验证其临床和商业潜力。在目标1下，169 Yb源将被构造成具有3 mm 3的 该体积沿着其控制导丝将能够重新激活。则预期 源/线将成功通过FDA许可所需的测试。在目标2下，169 Yb（再）激活 基于初步数据的模型将通过实验进行校准，这将适用于多达11次（重新）激活。 预期每次（重新）激活平均需要9天，平均临床源寿命 每次（重新）激活后41天。预计这一贡献将是重大的，因为它消除了一个主要的 阻碍改善近距离放射治疗，可能有利于前列腺癌和宫颈癌患者。这项工作是 创新，因为ReNeu源的体积增加了3 mm 3，结合低曲率RSBT 应用程序代表了一个实质性的偏离现状，独特的提供能力，成本- 有效地提供单次前列腺癌治疗和非侵入性治疗宫颈癌。