Endoskeletal nanodrops for x-ray acoustic dosimetry

项目总结 在美国，超过一半的癌症患者接受放射治疗(RT)作为其 癌症治疗(每年500,000名患者)。癌症患者通常会接受高度靶向的剂量 持续数天或数周的辐射。每个患者通常每天都会接受25-40次治疗。 治疗结果取决于准确的放射治疗。所有RT患者的治疗计划都是基于 在治疗开始前几天或几周进行计划的“模拟”CT扫描。然而，由于重量的原因， 在模拟和治疗之间的时间损失或肿瘤缩小，解剖变化可能导致健康 被照射的组织。照射健康组织的副作用可能是严重的。适应性 优化 有 机会来了。然而，ART的实施受到严重限制，因为缺乏 一种实时设备，可以准确测量患者体内的辐射分布。目前 不存在能够测量患者体内辐射剂量分布的系统。 RT(ART)-Re- 基于患者日常解剖的放射分布，以保持计划质量- 被认为是一种在减少正常组织损伤的情况下提供更多辐射的方法；增加 一种治愈方法，副作用更少 该项目将通过开发第一种用于成像放射治疗的造影剂来满足这一需求。我们的 这种方法将采用x射线声(XA)效应，类似于物理上的“光声效应”。 通过吸收脉冲光子的热能而产生声波的现象 波束。在XA计算机层析成像(XACT)中，光子束是由 医用直线加速器在临床放射治疗中的应用。需要新型XA造影剂 以改进XACT成像，并对我们的XACT剂量学概念至关重要。为此，我们 最近发明的可蒸发内骨骼滴剂(VEDs)包括液体氟碳液滴和固体 碳氢化合物“骨架”。我们发现液态氟碳液滴在加热和熔化时会蒸发。 碳氢化合物固体。液滴到气泡的膨胀发出一种声波，可以用 Xact，由此产生的微泡是超声成像的回声。该项目将开发VED 用于XACT的新型放射治疗造影剂的技术通过1)含有高z-VEDs的配方 碳氢化合物骨架相中的金属离子，以吸收X射线并刺激汽化；以及2) 高zVED的XA效应的测量。实现这些目标将使未来的商业化成为可能 活体临床前试验和临床翻译。

PROJECT SUMMARY More than half of all cancer patients in the United States receive Radiation Therapy (RT) as a part of their cancer treatment (>500,000 patients per year). Cancer patients typically receive a highly targeted dose of radiation over the course of days or weeks. Each patient will typically receive 25-40 daily treatments. Treatment outcome is dependent on accurate delivery of radiation. All RT patient treatment plans are based on a planning `simulation' CT scan, acquired days or weeks before the start of treatment. However, due to weight loss or tumor shrinkage in the time between simulation and treatment, anatomical changes may lead to healthy tissues being irradiated. Side effects of irradiating healthy tissue can be severe. Adaptive optimizing has chance . However, the implementation of ART is severely limited by the lack of a real-time device that can accurately measure the delivered radiation distribution within the patient. Currently no system exists which is capable of measuring the radiation dose distribution within the patient. RT (ART) – re- the radiation distribution based on the patient's daily anatomy in order to maintain the plan quality – been proposed as a means to deliver more radiation with reduced normal tissue damage; increasing the of a cure, with fewer side effects This project will address this need by developing the first contrast agent for imaging radiation therapy. Our approach will employ the x-ray acoustic (XA) effect, which is analogous to the “photoacoustic effect”, a physical phenomenon whereby acoustic waves are generated by the absorption of heat energy from a pulsed photon beam. In XA Computed Tomography (XACT), the photon beam is high-energy x-ray radiation generated by a medical linear accelerator (LINAC) used in clinical radiation therapy. Novel XA contrast agents are needed to improve XACT imaging and are essential to our concept of XACT dosimetry. Toward this end, we recently invented vaporizable endoskeletal drops (VEDs) comprising a liquid fluorocarbon droplet with a solid hydrocarbon “skeleton”. We discovered that the liquid fluorocarbon droplet vaporizes upon heating and melting of the hydrocarbon solid. The drop-to-bubble expansion emits an acoustic wave that can be imaged with XACT, and the resulting microbubble is echogenic for ultrasound imaging. This project will develop the VED technology into a novel radiation therapy contrast agent for XACT by 1) Formulation of VEDs comprising high-z metal ions within the hydrocarbon skeletal phase to absorb x-rays and stimulate vaporization; and 2) Measurement of the XA effect of high-z VEDs. Completing these aims will enable future commercialization, in vivo preclinical testing, and clinical translation.