Integration of non-invasive deep tissue microwave thermometry in the VectRx hyperthermia device in a transgenic liver tumor pig model

项目摘要/摘要 NeoTherma Oncology(NTO/www.nethermaoncology.com)开发了一种新的非侵入性医疗设备 将局部轻度高热(HT)作为标准护理治疗的辅助治疗 腹部深层肿瘤。VectRx™设备，被美国食品和药物管理局指定为“突破”，具有 在临床前研究中证明了其安全加热腹部器官(胰腺、肝脏、肾脏、脾)的能力 在健康的猪身上。FDA根据这些数据批准了VectRx的研究设备豁免 缺乏有效的胰腺癌大动物肿瘤模型。NTO在人类早期开创了第一个 马里兰大学医学中心的可行性研究(EFS)研究，以收集初步的安全性和性能 胰腺癌患者的数据。 在EFS的同时，NTO将与科罗拉多大学博尔德分校的研究人员合作，这些研究人员已经开发出 一种微波温度计(MT)，可用于非侵入性测量深层组织的温度。 这种发展是基于探测黑体辐射与温度成正比的能力，即 从皮肤到深层器官的不同组织深度释放。MTS的成功整合将有效地 提高VectRx的临床应用价值。这将解决有限的可获得性、访问权限、高 成本、后勤问题和对专业人员的依赖，就像磁共振的情况一样 测温仪。将设计、制造一系列MTS和辐射计，并将其集成到VectRx中 调整电势VectRx线圈以1)实现与操作兼容的有源和无源MTS设计 在VectRx内(开和关)；2)管理MTS、线圈失谐、E场和H场模式的任何潜在加热 VectRx操作期间的完整性。经过共同开发和优化，MTS的性能将是 在肝细胞癌(HCC)OnCopig模型中建立，精度目标为1.5°C。 存活率低且只有一小部分(15%)新诊断患者符合条件的疾病 因诊断较晚而导致的根治疗法。该模型适用于NTO的深部指示管线 腹部肿瘤，NTO之前已经完成了VectRx设备的安装并进行了 伊利诺伊大学兽医团队对3只肝癌肿瘤猪进行了初步工作，以优化超声- 引导手术放置光纤探头，用于关联MTS测量的温度。 尽管已知轻度高温的好处，但由于技术上的原因，它在美国还没有被广泛采用 目前的技术在解决深部、难以加热的肿瘤和缺乏体温测量方面存在局限性。在这 第一阶段项目，我们将证明这些关键的缺陷可以通过集成新的 VectRx的基于微波的温度技术，提供先进的创新演示 大动物肿瘤模型深部组织中高温的温度监测。

Project Summary/Abstract NeoTherma Oncology (NTO/www.neothermaoncology.com) has developed a novel non-invasive medical device that delivers mild hyperthermia (HT) loco-regionally as adjuvant therapy to standard of care treatment of abdominal deep-seated tumors. The VectRx™ device, designated “Breakthrough” by the FDA, has demonstrated its ability to safely heat abdominal organs (pancreas, liver, kidney, spleen) in pre-clinical studies in healthy swine. FDA approved an investigational device exemption for VectRx on the basis of these data and the lack of a validated large animal tumor model for pancreatic cancer. NTO has initiated a First in Human early feasibility study (EFS) study at the University of Maryland Medical Center to collect initial safety and performance data in pancreatic cancer patients. In parallel to the EFS, NTO will collaborate with University of Colorado-Boulder researchers who have developed a microwave thermometer (MT) that could be utilized to non-invasively measure temperatures in deep tissue. This development is based on the ability to detect the black body radiation proportional to temperature that is emitted at different tissue depths from skin to deep organ. Successful integration of the MTs will effectively improve the clinical utility of VectRx. This will address challenges posed by the limited availability, access, high cost, logistical concerns and reliance on specialized personnel, as is the case with magnetic resonance thermometry. A series of MTs and a radiometer will be designed, fabricated, and integrated into VectRx with potential VectRx coil adjustments to 1) achieve compatible designs of active and passive MTs with operation within VectRx (on and off); 2) manage any potential heating of the MTs, coil detuning, E-field and H-field pattern integrity during VectRx operation. Following co-development and optimization, the MTs’s performance will be established in a hepatocellular carcinoma (HCC) Oncopig model with an accuracy goal of 1.5°C. HCC is a disease with low survival rates and only a small fraction (15%) of newly diagnosed patients are eligible for curative treatments due to late diagnosis. The model is relevant to NTO’s indication pipeline of deep-seated abdominal tumors, and NTO has previously completed installation of the VectRx device and performed preliminary work in 3 HCC Oncopigs with the veterinary team at the University of Illinois to optimize ultrasound- guided surgical placement of fiberoptic probes that will be used to correlate temperatures measured by the MTs. Despite the known benefits of mild HT, it has not been widely adopted in the US because of the technical limitations of current technologies to address deep, hard to heat tumors and the lack of thermometry. In this Phase I project, we will demonstrate that these critical deficiencies can be overcome through integration of novel microwave-based temperature techniques with VectRx, providing an innovative demonstration of advanced temperature monitoring of HT in deep tissue in a large animal tumor model.