Discrete Sensor Devices for Determining Cancer Targets

该项目的长期目标是为临床实践带来一种用于癌症相关分析物的实时和非侵入性测量的新技术。该技术由在肿瘤活检时植入的传感器组成，以允许随后通过磁共振方法监测肿瘤分析物，例如pH和p02。该项目的具体目标如下：设计和执行临床前研究，以支持向FDA提交的Premarl批准申请，并开发一种新的传感器构建方法。传感器将首先在小鼠模型中进行验证，该小鼠模型被设计为显示pH传感器对化疗的不同响应，以及在p02传感器的情况下对辐射的时间响应。这些模型将允许将传感器测量与小鼠中的治疗功效相关联，并提供设备的体内验证。随后将在患有内源性肿瘤的犬中进行临床前研究，以在实际犬受试者中测试该设备，这是一个特别重要的步骤，因为犬肿瘤模型 表现出与人类癌症相似的生物学行为。这些研究的结果将为向FDA提交的上市前批准申请提供支持性证据。该项目的第二个目标是开发两种微创传感器格式，与当前传感器尺寸相比，其尺寸更小。这些格式中的每一种都将为设备提供不同的优势。活检植入式传感器配有线圈，将允许阅读设备，而无需使用昂贵的MRI扫描仪，而可注射传感器将简化设备的植入程序，而无需手术或活检。 活检植入式传感器将在体外和体内通过使用台式单侧NMR测量pH值进行验证，使用为第一个特定目标开发的小鼠模型。可注射传感器将由3个部分组成，这3个部分可以同时进行研究：含有传感剂的半渗透性微球的制造;可注射装置基质的开发;以及装置的尺寸和形状的原位控制。该器械将在体外和体内进行确认，与活检植入式传感器相似。

The long-term objective of this project is to bring to clinical practice a novel technology for the real-time and non-invasive measurement of cancer-related analytes. This technology consists of a sensor implanted at the time of a tumor biopsy to allow subsequent monitoring of tumor analytes such as pH and p02 through magnetic resonance methods. The specific aims of the project are as follows: design and execute preclinical studies in support of a Premarl<et Approval Application to the FDA, and develop a new approach to construction of the sensors. Sensors will first be validated in a mouse model designed to show differential response to chemotherapy for the pH sensor, and temporal response to irradiation in the case of the p02 sensor. These models will allow the correlation of sensor measurements to therapeutic efficacy in mice and provide in vivo validation of the devices. A preclinical study in dogs with endogenous tumors will then follow to test the devices in actual canine subjects, a particularly important step given that canine tumor models exhibit biological behavior similar to human cancers. Results from these studies will provide supporting evidence for a Premarket Approval Application to the FDA. The second aim in this project is the development of two minimally-invasive sensor formats with reduced dimensions compared to the current sensor size. Each of these formats will afford a different advantage to the device. The biopsy-implantable sensor, fitted with a coil, will allow reading of the device without the use of a costly MRI scanner, while the injectable sensor will simplify the implantation procedure ofthe device, without requiring surgery or a biopsy. The biopsy-implantable sensor will be validated in vitro and in vivo by pH measurements with a benchtop one-sided NMR, using the mouse model developed forthe first specific aim. The injectable sensor will consist of 3 parts which may be investigated concurrently: fabrication of semi-permeable microspheres containing the sensing agent; development ofthe injectable device matrix; and in situ control ofthe size and shape of the device. The device will be validated in vitro and in vivo similarly to the biopsy-implantable sensor.