Preclinical Efficacy of Silicon-based Dual Energy CT Contrast Material

硅基双能CT造影材料的临床前疗效

• 批准号: 8833135
• 负责人: William Guerin Bradley
• 金额: $ 23.34万
• 依托单位: NEXTRAST, INC.
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-16 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8833135
• 关键词: Abdomen; Abscess; Adopted; American; Anatomy; Animal Model; Attenuated; Barium; Biocompatible; Blood Vessels; Calculi; Clinical; Color; Complex; Contrast Media; Cost Savings; Data; Development; Diagnosis; Diagnostic; Diagnostic Errors; Disease; Dose; Drug Formulations; Drug Kinetics; Effectiveness; Emergency Situation; Enteral; FDA approved; Foundations; Gastrointestinal Diseases; Goals; Head; Health Care Costs; Healthcare Systems; Hemorrhage; Image; In Vitro; Individual; Inflammatory; Intestines; Intravenous; Iodine; Ischemia; Low Dose Radiation; Measures; Medical; Medical Errors; Oral; Oranges; Organ; Outcome; Phase; Polymers; Preclinical Testing; Property; Protocols documentation; Radiation; Rattus; Research; Resolution; Roentgen Rays; Route; Rupture; Safety; Scanning; Series; Signal Transduction; Silicon; Silicones; Small Business Technology Transfer Research; Speed; Testing; Tomography, Computed, Scanners; Toxic effect; Trauma; X-Ray Computed Tomography; absorption; base; commercialization; cost; drug development; high risk; improved; in vivo; novel; pre-clinical; preclinical efficacy; preclinical evaluation; public health relevance; radiologist; soft tissue; uptake

DESCRIPTION (provided by applicant): Our long term goal is to revolutionize the safety and effectiveness of computed tomography (CT) imaging for millions of Americans across a broad range of gastrointestinal disease. Bowel and intravenous contrast materials improve the CT imaging of abdominal disease. Unfortunately, none of the current clinical contrast materials are visibly different from the others at imaging, even on modern dual energy CT (DECT) scanners, because all agents are based on iodine or barium which attenuate X-rays similarly across different X-ray spectra. This limitation leads to ambiguous images that cost over $2B in medical errors annually in the USA. We now have dramatic preclinical in vivo data showing that novel oral silicone materials can be delivered concurrently with yet be easily differentiated from current iodinated intravenous agents to produce simultaneous, high-resolution, perfectly co-registered CT images of the bowel and vasculature in a single pass of the DECT scanner. Such double contrast-enhanced DECT scans give rich abdominal anatomic detail at lower radiation dose than a conventional CT scan, eliminate protocol errors, increase the speed of diagnosis, and will dramatically reduce health care costs. Our agent is disruptive because silicone has not previously been described as an X-ray attenuating material for CT contrast agents. Since DECT scanners are already clinically available and conventional enteric contrast is already widely used, a dramatically improved silicone enteric contrast should be rapidly adopted once FDA approved. Our overall hypothesis is that a novel silicone contrast agent is safe, reduces radiation dose, and provides richly detailed anatomic images in a single DECT scan that cannot be achieved with conventional CT contrast agents. The Specific Aims of our project are to test the hypotheses that 1) Enteric silicone contrast agents show minimal if any systemic uptake; 2) CT scans obtained with enteric silicone-based contrast material and automated exposure control require less radiation dose than with conventional enteric contrast agents; 3) DECT obtained with enteric CT contrast and intravenous iodinated contrast provide substantially more information on contrast material concentration and distribution than when obtained with conventional barium and iodinated agents in vitro and in vivo. These key data will be the foundation for subsequent development of this powerful DECT agent to catalyze a frame-shift in CT imaging that will increase the speed, accuracy, and confidence of CT imaging diagnosis for everyday abdominal scenarios with reduced cost to the healthcare system and lower radiation dose.

描述（由申请人提供）：我们的长期目标是彻底改变计算机断层扫描（CT）成像的安全性和有效性，为数百万美国人提供广泛的胃肠道疾病。肠道和静脉造影剂可改善腹部疾病的CT成像。不幸的是，即使在现代双能CT（DECT）扫描仪上，当前的临床对比材料在成像时也没有与其他对比材料明显不同，因为所有试剂都基于碘或钡，碘或钡在不同的X射线光谱上类似地衰减X射线。这种限制导致模糊的图像，在美国每年的医疗错误成本超过20亿美元。我们现在有大量的临床前体内数据表明，新型口腔硅胶材料可以与当前的碘化静脉注射剂同时输送，但很容易与其区分开来，从而在DECT扫描仪的单次通过中产生肠和血管系统的同步、高分辨率、完美配准的CT图像。这种双重对比增强的DECT扫描以比传统CT扫描更低的辐射剂量提供丰富的腹部解剖细节，消除协议错误，提高诊断速度，并将大大降低医疗保健成本。我们的试剂是破坏性的，因为硅胶以前没有被描述为CT造影剂的X射线衰减材料。由于DECT扫描仪已经在临床上可用，并且传统的肠道造影剂已经广泛使用，一旦FDA批准，应迅速采用显著改进的硅胶肠道造影剂。我们的总体假设是，一种新型硅胶造影剂是安全的，可降低辐射剂量，并在单次DECT扫描中提供丰富详细的解剖图像，这是传统CT造影剂无法实现的。我们项目的具体目的是检验以下假设：1）肠道硅胶造影剂显示出最小的全身摄取（如果有）; 2）使用肠道硅胶造影剂和自动曝光控制获得的CT扫描需要的辐射剂量低于传统肠道造影剂;第三章用肠道CT造影剂和静脉内碘化造影剂获得的DECT提供了关于造影剂浓度的更多信息，在体外和体内，与使用常规钡和碘化剂获得的分布相比，这些关键数据将成为后续开发这种强大的DECT试剂的基础，以促进CT成像的帧移，从而提高日常腹部场景CT成像诊断的速度，准确性和信心，降低医疗保健系统的成本和辐射剂量。