Ultrasonic assessment of therapeutic response

描述(由申请人提供)：在这项提案中，我们寻求开发一套新的工具来评估和增强具有直接临床意义的抗癌治疗的有效性。特别是，我们已经开发并嵌入了实时定量参数超声成像血管体积/密度和流速的方法，以在临床扫描仪中评估肿瘤治疗，并将在这里评估和验证这些方法。我们的疗效评估目标包括：评估在评估疗效时使用超声波方法估计血流速度和血管体积/密度的情况；将这些方法移植到实时扫描测量中；结合组织学使用超声波反馈，以适当药物的鸡尾酒优化治疗。此外，我们努力通过增加血管通透性和纳米颗粒积累使用超声波来提高治疗效果。在我们最初的研究中，我们使用低热剂量的2分钟辐射，我们发现脂质体在辐照的肿瘤中的积聚增加了~3倍，高达22%ID/g，并且在辐照的肌肉或淋巴结中的积聚增加了3-10倍。在我们的网站和其他地方，消融治疗和纳米药物给药的组合已经开始，随着磁共振引导的超声进入临床，这种组合将被更频繁地使用。我们使用超声波提高疗效的目的是：确定超声增强血管通透性增加的机制；最大限度地利用超声波增强肿瘤及周围组织中颗粒的蓄积；建立描述超声增强通透性的药代动力学模型；以及比较超声前后注射颗粒的疗效，并将超声增强释放纳入包括抗血管生成药物、化疗药物和超声反应监测在内的策略中。与公共卫生相关：目前，美国四分之一的死亡是由癌症引起的。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疗效评估战略的开发，该战略提供定量、可重复和用户独立的措施。此外，我们正在开发通过增强药物在肿瘤内的积累来提高使用超声波的治疗效果的方法。

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.