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

通过新标记物对肿瘤血管进行 MRI 和近红外成像

• 批准号: 8240999
• 负责人: AURELIAN RADU
• 金额: $ 22.12万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-03-11 至 2014-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8240999
• 关键词: Affect; Antibodies; Antineoplastic Agents; Area; Binding; Blood Vessels; Cancer Model; Categories; Cell Culture Techniques; Cell surface; Cells; Clinical; Clinical Trials; Contrast Media; Coupled; Data; Detection; Development; Drug Delivery Systems; Early Diagnosis; Electron Microscopy; Emulsions; Endothelial Cells; Ensure; Fluorescence; Follicle Stimulating Hormone Receptor; Gold; Gonadal structure; Human; Image; Imagery; Imaging Techniques; Immune; Immunoglobulin G; Injection of therapeutic agent; Integrins; Lead; Ligands; Location; Magnetic Resonance Imaging; Malignant Neoplasms; Manuscripts; Monitor; Mus; Neoplasms in Vascular Tissue; New Agents; Normal tissue morphology; Nude Mice; Oils; Optics; Particle Size; Performance; Pharmaceutical Preparations; Phase; Procedures; Process; Publications; Quantum Dots; Reporting; Research Personnel; Screening procedure; Signal Transduction; Solid; Staging; Surface; Testing; Therapeutic Intervention; Tumor Markers; Water; Work; base; cancer therapy; clinical application; density; imaging modality; iron oxide; nanoparticle; nanoparticulate; neoplastic cell; novel marker; optical imaging; particle; physical property; process optimization; public health relevance; receptor; research study; success; tumor; whole body imaging/scanning

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.

描述（由申请人提供）：早期诊断和监测治疗干预效果都需要更好的肿瘤成像方法。在正在开发的各种成像策略中，一个非常有前途的类别是基于构成肿瘤血管壁的内皮细胞（EC）表面上存在的标记。近年来报道了许多肿瘤 EC 标志物，但迄今为止还没有一个被证明足够适合大规模临床使用。我们最近发现了一种新的肿瘤 EC 标志物，它存在于所分析的所有人类肿瘤类型中，包括早期和晚期，并且在除性腺的某些区域之外的所有正常组织中都不存在。根据我们迄今为止掌握的信息，该标记可能是比当前可用的任何标记更好的成像目标。该项目旨在证明该标记物可用于小鼠癌症模型中肿瘤的近红外和磁共振成像（MRI）。第一个目标在于纳米颗粒成像剂的合成和表征及其在细胞培养物中的测试。该纳米颗粒由氧化铁核心水包油乳液组成，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，并根据物理特性进行表征。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。第二个目标是在携带注射人类肿瘤细胞后形成的肿瘤的裸鼠中测试靶向造影剂。药剂将通过静脉注射方式输送。注射。所提出的靶向成像程序旨在构成后续临床试验的基础。所提出的成像策略有可能成为通过单次全身成像扫描早期检测大多数实体癌的通用程序，无论其类型和位置如何。 公共健康相关性：我们建议开发一种新的磁共振成像（MRI）药剂，通过新发现的肿瘤标志物靶向肿瘤，该标志物存在于大多数人类肿瘤类型的血管表面，但正常组织中不存在。该项目有可能引入一种通用筛查程序，允许在单次治疗中使用单一显像剂检测大多数肿瘤类型，无论其在体内的位置如何，并且在抗癌治疗的早期阶段有更高的成功机会。