Preclinical Efficacy of Silicon-based Dual Energy CT Contrast Material

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，目前的临床造影剂在成像方面也没有明显的不同，因为所有的造影剂都是基于碘或钡的，它们在不同的x射线光谱上对x射线的衰减相似。这一限制导致图像模糊，每年在美国造成超过20亿美元的医疗差错。我们现在有显著的临床前体内数据表明，新型口服硅胶材料可以与目前的碘静脉注射药物同时使用，但很容易与之区分，从而在DECT扫描仪的一次扫描中产生同时、高分辨率、完美共注册的肠道和血管CT图像。与传统的CT扫描相比，这种双重对比增强的DECT扫描以更低的辐射剂量提供了丰富的腹部解剖细节，消除了方案错误，提高了诊断速度，并将大大降低医疗成本。我们的造影剂是破坏性的，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，传统的肠道造影剂已经被广泛使用，一旦FDA批准，一种显著改进的硅胶肠道造影剂应该迅速被采用。我们的总体假设是，一种新型硅树脂造影剂是安全的，减少了辐射剂量，并在单次DECT扫描中提供了传统CT造影剂无法实现的丰富详细的解剖图像。我们项目的具体目的是测试以下假设：1)肠道硅酮造影剂显示最小的（如果有的话）系统摄取；2)使用肠内硅基造影剂和自动暴露控制获得的CT扫描比使用常规肠内造影剂所需的辐射剂量更小；3)肠道CT造影剂和静脉碘化造影剂获得的DECT比常规钡和碘化造影剂在体内和体外获得的造影剂浓度和分布信息多得多。这些关键数据将成为后续开发这种强大的DECT试剂的基础，以催化CT成像的框架转换，从而提高CT成像诊断的速度，准确性和信心，以减少医疗保健系统的成本和降低辐射剂量。

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.