Ultrasonic assessment of therapeutic response

描述（由申请人提供）：在本提案中，我们寻求开发一套新工具，以评估和增强具有直接临床相关性的抗癌疗法的疗效。特别是，我们已经开发并嵌入了血管体积/密度和流速的实时定量参数超声成像方法，以评估临床扫描仪中的肿瘤治疗，并将在这里评估和验证这些方法。我们评估治疗效果的目的包括：评价超声方法在评估治疗反应中估计流速和血管体积/密度的使用;将方法迁移到实时扫描仪测量;以及使用超声反馈与组织学结合使用适当药物的鸡尾酒来优化治疗。此外，我们奋进通过使用超声增加血管渗透性和纳米颗粒积聚来增强治疗功效。在我们使用低热剂量的2分钟声处理的初始研究中，我们发现在声处理的肿瘤中脂质体的积累增加约3倍至高达22%ID/g，并且在声处理的肌肉或淋巴结内的积累增加3-10倍。在我们的研究中心和其他研究中心，消融治疗和纳米颗粒药物给药的组合已经开始，随着MR引导超声进入临床，这种组合将更频繁地使用。我们的目标是提高超声的功效是：确定超声增强血管通透性增加的机制;最大限度地提高超声增强颗粒在肿瘤和周围组织中的积聚;建立描述超声增强通透性的药代动力学模型;并比较在超声之前和之后立即注射颗粒的功效，并结合US-增强输送到一个战略，包括抗血管生成药物，化疗药物和超声波监测的反应。公共卫生相关性：目前，在美国，四分之一的死亡是由于癌症。可以采用许多新的治疗策略;然而，需要有效的方法来测试这些策略。我们正在完成基于超声的治疗效果评估策略的开发，该策略提供定量、可重复和独立于用户的测量。此外，我们正在开发使用超声通过增强肿瘤内药物的积累来提高治疗效果的方法。

DESCRIPTION (provided by applicant): In this proposal, we seek to develop a set of new tools to assess and enhance the efficacy of anti-cancer therapies that have immediate clinical relevance. In particular, we have developed and embedded methods for real-time quantitative parametric ultrasound imaging of vascular volume/density and flow rate to assess tumor therapies in a clinical scanner and will evaluate and validate those methods here. Our aims for the assessment of therapeutic efficacy include: evaluate the use of ultrasound methods to estimate flow rate and vascular volume/density in the assessment of therapeutic response; migrate the methods to real-time, on-scanner measurement; and use ultrasound feedback together with histology to optimize treatment with a cocktail of appropriate drugs. Further, we endeavor to enhance therapeutic efficacy by increasing vascular permeability and nanoparticle accumulation using ultrasound. In our initial studies using 2-minute insonation with a low thermal dose, we found that accumulation of liposomes in an insonified tumor increases ~three-fold to as much as 22%ID/g and the accumulation within insonified muscle or lymph nodes increased 3-10 fold. At our site and others the combination of ablative therapies and nanoparticle drug administration has already begun and as MR-guided ultrasound enters the clinic, this combination will be used more frequently. Our aims for the enhancement of efficacy with ultrasound are to: determine the mechanism for ultrasound-enhanced increases in vascular permeability; maximize ultrasound enhancement of the accumulation of particles in a tumor and surrounding tissue; establish a pharmacokinetic model that describes ultrasound-enhanced permeability; and compare the efficacy of particle injection immediately before and after ultrasound and incorporate US- enhanced delivery into a strategy that includes an anti-angiogenic drug, chemotherapeutics an ultrasound monitoring of response. PUBLIC HEALTH RELEVANCE: Currently, one in 4 deaths in the United States is due to cancer. Many new therapeutic strategies can be employed; however, efficient methods to test these strategies are required. We are completing the development of an ultrasound-based strategy for the assessment of therapeutic efficacy that provides quantitative, repeatable and user-independent measures. Further, we are developing methods to enhance therapeutic efficacy using ultrasound by enhancing the accumulation of drug within the tumor.