Biodegradable macromolecular CT contrast agents

可生物降解高分子CT造影剂

基本信息

批准号：
8870352
负责人：
ZHENG-RONG LU
金额：
$ 23.3万
依托单位：
CASE WESTERN RESERVE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-09-01 至 2017-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8870352
关键词：
Acute Address Adverse effects Animal Model Animals Blood Blood Circulation Blood Vessels Cardiovascular system Clinical Clinical Protocols Contrast Media Data Development Diagnostic Diagnostic Imaging Diagnostic radiologic examination Dose Effectiveness Elements Excretory function Filtration Future Goals Half-Life Health Heavy Metals Image In Vitro Incidence Injection of therapeutic agent Intervention Investigation Kidney Kidney Diseases Malignant Neoplasms Measures Modeling Modification Molecular Molecular Weight Oryctolagus cuniculus Perfusion Radiation Reporting Research Project Grants Roentgen Rays Safety Technology Testing Time X-Ray Computed Tomography assault attenuation base body system cancer imaging cardiovascular imaging clinical application contrast enhanced contrast imaging copolymer coronary computed tomography angiography design dosage image guided intervention imaging modality improved in vivo intravenous injection nanoparticle nanosized novel polysulfide soft tissue tumor tumor progression

项目摘要

DESCRIPTION (provided by applicant): The goal of this research project is to design and develop novel iodinated polysulfides as biodegradable macromolecular blood pool X-ray computed tomography (CT) contrast agents. There is an unmet clinical need for safe and effective blood pool contrast agents for clinical diagnostic imaging and image-guided interventions. Currently clinical agents have a transient blood half-life. High dose and multiple injections are often used to generate sufficient contrast enhancement in many clinical protocols. However, high dose may cause contrast-induced nephropathy. Although nanosized CT have agents have been reported, their clinical use is limited by the safety concerns associated their slow clearance from the body. In this exploratory research project, we propose to develop novel biodegradable macromolecular blood pool CT contrast agents to address the limitations of clinical CT agents and nanosized agents and the unmet clinical need. We will first design, synthesize and characterize iodinated polysulfides as biodegradable macromolecular blood pool CT contrast agents and determine their in vitro and in vivo degradability and clearance in an animal model in the specific aim 1, and then determine the effectiveness of the novel blood pool CT contrast agents for cardiovascular imaging, cancer imaging and quantitative perfusion imaging in an animal tumor model in the specific aim 2. Our long-term goal is to develop a safe and effective biodegradable macromolecular blood pool CT contrast agent for clinical cardiovascular imaging, cancer imaging, perfusion imaging and image- guided interventions.

描述（由申请人提供）：本研究项目的目标是设计和开发新型碘化多硫化物作为可生物降解的大分子血池X射线计算机断层扫描（CT）造影剂。用于临床诊断成像和图像引导干预的安全有效的血池造影剂的临床需求尚未得到满足。目前临床药物的血液半衰期是短暂的。在许多临床方案中，通常使用高剂量和多次注射来产生足够的对比度增强。然而，高剂量可能会导致造影剂肾病。尽管纳米级 CT 药物已有报道，但由于其从体内清除缓慢相关的安全问题，其临床应用受到限制。在这个探索性研究项目中，我们建议开发新型可生物降解的高分子血池CT造影剂，以解决临床CT造影剂和纳米造影剂的局限性以及未满足的临床需求。我们将首先设计、合成和表征碘化多硫化物作为可生物降解的高分子血池CT造影剂，并在特定目标1的动物模型中确定其体外和体内的降解性和清除率，然后确定新型血池CT的有效性造影剂用于动物肿瘤模型中的心血管成像、癌症成像和定量灌注成像，具体目标2。我们的长期目标是开发一种安全有效的可生物降解的高分子血池CT造影剂临床心血管成像、癌症成像、灌注成像和图像引导干预。