Biodegradable macromolecular CT contrast agents

描述（由申请人提供）：本研究项目的目的是设计和开发新型碘化多硫化物作为生物可降解大分子血池X射线计算机断层扫描（CT）造影剂。对于用于临床诊断成像和图像引导介入的安全有效的血池造影剂存在未满足的临床需求。目前，临床药物具有短暂的血液半衰期。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，高剂量可能导致造影剂诱导的肾病。尽管已经报道了纳米尺寸的CT具有药剂，但是它们的临床使用受到与它们从身体缓慢清除相关的安全性问题的限制。在这个探索性的研究项目中，我们提出开发新的生物可降解的大分子血池CT造影剂，以解决临床CT剂和纳米制剂的局限性和未满足的临床需求。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大分子血池CT造影剂，并在特定目标1中在动物模型中确定它们的体外和体内降解性和清除率，然后在特定目标2中在动物肿瘤模型中确定新型血池CT造影剂用于心血管成像、癌症成像和定量灌注成像的有效性。我们的长期目标是开发一种安全有效的可生物降解的大分子血池CT造影剂，用于临床心血管成像、癌症成像、灌注成像和图像引导介入。

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.