MRI AND NEAR-INFRARED IMAGING OF THE TUMOR VASCULATURE VIA A NEW MARKER

描述(由申请人提供)：为了早期诊断和监测治疗干预的效果，需要更好的肿瘤成像方法。在正在开发的各种成像策略中，一个非常有希望的类别是基于构成肿瘤血管壁的内皮细胞(ECs)表面的标记。近年来已经报道了一些肿瘤EC标记物，但到目前为止还没有一种被证明足够好，可以大规模临床应用。我们最近发现了一种新的肿瘤EC标记物，它存在于所有被分析的人类肿瘤类型中，无论是早期还是晚期，除了性腺的一些区域外，在所有正常组织中都不存在。根据我们目前掌握的信息，这个标记可能是一个比目前任何可用的标记都更好的成像目标。本项目旨在证明该标记物可用于小鼠肿瘤模型的近红外和磁共振成像(MRI)。第一个目标是纳米粒子显像剂的合成和表征，以及它们在细胞培养中的测试。这种纳米粒子由氧化铁为核心的水包油乳剂组成，可用于靶向成像和抗癌药物的输送。这些颗粒将与针对EC表面标记的抗体进行化学偶联，并将根据物理性质进行表征。纳米颗粒与培养细胞表达的标记物结合并产生荧光和MRI信号的能力也将得到验证。第二个目标是在裸鼠身上测试靶向造影剂，这些裸鼠携带的肿瘤是在注射人类肿瘤细胞后发展起来的。代理人将由静脉注射运送。注射。拟议的靶向成像程序旨在构成后续临床试验的基础。拟议的成像策略有可能导致通过一次全身成像扫描早期发现大多数实体癌症的一般程序，而不考虑它们的类型和位置。 公共卫生相关性：我们建议开发一种新的磁共振成像(MRI)试剂，通过新发现的肿瘤标记物来靶向肿瘤，该标记物存在于大多数人类肿瘤类型的血管表面，而在正常组织中缺失。该项目有可能引入一种通用的筛查程序，允许在单一疗程中使用单一显像剂检测大多数肿瘤类型，而不考虑它们在体内的位置，并在抗癌治疗成功率高得多的早期阶段进行检测。

DESCRIPTION (provided by applicant): Better tumor imaging methods are needed both for early diagnosis and for monitoring the effects of therapeutic interventions. Among various imaging strategies under development, a very promising category is based on markers present on the surface of the endothelial cells (ECs) that constitute the walls of the tumor blood vessels. A number of tumor EC markers have been reported in recent years but none proved so far good enough for large scale clinical use. We discovered recently a new tumor EC marker that is present in all tumor human tumor types analyzed, both early and advanced, and absent from all normal tissues except some areas of the gonads. Based on the information we have so far, this marker could be a better imaging target than any of the currently available. This project is aimed at demonstrating that the marker can be used for near infrared and magnetic resonance imaging (MRI) of tumors in mouse cancer models. The first aim consists in the synthesis and characterization of nanoparticulate imaging agents and their testing in cell cultures. The nanoparticles consist of an iron oxide core oil-in-water emulsion, which can be used for both targeted imaging and for delivery of anticancer drugs. The particles will be chemically coupled to antibodies against the EC surface marker and will be characterized in terms of physical properties. The ability of the nanoparticles to bind to the marker expressed by cells in culture and generate fluorescence and MRI signals will be also verified. The second Aim is to test the targeted contrast agents in nude mice that carry tumors that develop after injection of human tumor cells. The agents will be delivered by i.v. injection. The proposed targeted imaging procedures are intended to constitute the basis for subsequent clinical trials. The proposed imaging strategy has the potential to lead to a general procedure for early detection of the majority of solid cancers, independently of their type and location, by a single whole-body imaging scan. PUBLIC HEALTH RELEVANCE: We propose to develop a new magnetic resonance imaging (MRI) agent, targeted to tumors by a newly discovered tumor marker that is present on the surface of the blood vessels in most human tumor types and absent from normal tissues. The project has the potential to introduce a general screening procedure that would allow the detection, in a single session and using a single imaging agent, of most tumor types, independently of their location in the body, and at an early stage, when anticancer therapies have much higher chances of success.