Biodegradable macromolecular CT contrast agents

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。临床对安全有效的血池造影剂用于临床诊断成像和图像引导干预的需求尚未得到满足。目前临床药物的血液半衰期是短暂的。在许多临床方案中，经常使用高剂量和多次注射来产生足够的对比增强。然而，高剂量可引起造影剂肾病。尽管纳米级CT具有显像剂的报道，但由于其从体内清除缓慢的安全性问题，其临床应用受到限制。在本探索性研究项目中，我们提出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造影剂和纳米级造影剂的局限性和临床未满足的需求。我们将首先设计、合成并表征作为可生物降解的大分子血池CT造影剂的碘化多硫化物，并在特定目标1中确定其在动物模型中的体外和体内降解性和清除率，然后在特定目标2中确定新型血池CT造影剂在动物肿瘤模型中用于心血管成像、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干预。

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.