Biodegradable macromolecular CT contrast agents

描述(申请人提供)：本研究项目的目标是设计和开发新型的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。临床上对安全有效的血池造影剂的需求尚未得到满足，这些造影剂用于临床诊断、成像和影像引导干预。目前，临床药物有短暂的血液半衰期。在许多临床方案中，经常使用大剂量和多次注射来产生足够的对比增强。然而，大剂量可能会导致造影剂肾病。尽管已有纳米级CTHAS试剂的报道，但由于其在体内的缓慢清除，其安全性问题限制了它们的临床应用。在这一探索性研究项目中，我们建议开发新型可生物降解的大分子血池CT造影剂，以解决临床CT剂和纳米造影剂的局限性和未满足的临床需求。我们将首先设计、合成和表征可生物降解的大分子血池CT造影剂，并测定其在体外和体内的降解性和在动物模型中的清晰度。2.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、肿瘤成像、灌注成像和图像引导介入治疗。

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.