Real Time Visualization of Clot under X-Ray Using "Clot-Paint", a Novel Iodinated

使用新型碘化物“Clot-Paint”在 X 射线下实时观察血块

基本信息

批准号：
7913705
负责人：
LUCJAN J J HRONOWSKI
金额：
$ 18.2万
依托单位：
BIOPSY SCIENCES, LLC
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-06-15 至 2011-12-14
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7913705
关键词：
Ablation Academia Acute Affinity Animal Model Animal Testing Animals Applications Grants Arizona Arteries Binding Binding Proteins Biopsy Blood Vessels Catheters Clinical Clinical Research Coagulation Process Contrast Media Coronary Thrombosis Cytolysis Detection Devices Doctor of Philosophy Excision Funding Goals Grant Hemorrhage Hour Human Image Imagery In Vitro Industry Injection of therapeutic agent Institution Intervention Intravenous Investigation Iodides Iodine Lasers Lead Measurement Measures Mechanics Medical Methods Monitor Oryctolagus cuniculus Paint Patients Penetration Peptides Peripheral Phase Physicians Polymer Chemistry Positioning Attribute Preparation Procedures Process Proteins Reperfusion Therapy Research Retrieval Risk Roentgen Rays Saline Science Side Site Small Business Innovation Research Grant Societies Solutions Speed Stroke Symptoms System Testing Thrombectomy Thrombosis Thrombotic Stroke Thrombus Time United States National Institutes of Health Universities X-Ray Computed Tomography abstracting amino group attenuation carboxyl group commercialization cost cost effective design experience femoral artery in vivo minimally invasive novel polypeptide public health relevance radiologist receptor receptor binding scale up time interval

项目摘要

DESCRIPTION (provided by applicant): Biopsy Sciences, LLC NIH SBIR Phase I Grant Application Real Time Visualization of Clot under X-Ray Using "Clot-Paint", a Novel Iodinated Protein Receptor Bound Molecule Project Summary/Abstract There are over 750,000 new cases of stroke in the U.S. each year. Of those suffering a major stroke, one-third will recover, one-third will die and one-third will be permanently impaired. The costs to society to treat stroke patients exceed $58 billion dollars a year in the U.S. Current acute embolic stroke treatment options include intravenous TPA administered within 3 hours after symptoms appear, intra-arterial TPA within 6 hours after the stroke onset and mechanical thrombectomy using the FDA cleared MERCI L5 retrieval system up to 6 hours and possibly longer after symptoms appear. Other clot retrieval/ablation devices (AngioJet, Latis laser device, EPAR laser, Penumbra system, Neuoronet snare) are under investigation but are not commercially available. Clot removal is the ideal treatment because of the speed of reperfusion and the lower risk of bleeding. We believe that ability to see the clot in real time during the intervention will help to shorten the time to clot removal and expand the number of physicians willing to participate in treating embolic strokes. Lysis alone can take up to 3 hours to dissolve the clot where clot removal can be performed in less than 30 minutes. Our long term objective is to introduce a novel contrast agent, "Clot-Paint" that is injected onto the clot through a catheter placed into the occluded artery. Clot-Paint adheres tightly to the intra-arterial thrombus via protein receptor sites while at the same time containing sufficient iodine molecules rendering the clot opaque to the x-ray beam and visible under fluoroscopic imaging for an extended period of time. This new molecule is composed of a clot binding protein and iodinated molecules. This novel contrast agent will allow the neurointerventional radiologist or cardiologist to visualize the clot with real time fluoroscopic imaging, thus allowing for accurate device positioning into the clot and to confirm successful clot capture into the device before removal. In addition, any clot fragments that migrate downstream could be readily identified and removed. Discussions with doctors who currently perform stroke intervention about this new contrast agent have confirmed the high potential clinical utility of such a novel contrast agent. PUBLIC HEALTH RELEVANCE: Biopsy Sciences, LLC NIH SBIR Phase I Grant Application Real Time Visualization of Clot under X-Ray Using "Clot-Paint", a Novel Iodinated Protein Receptor Bound Molecule Project Narrative There are over 750,000 new cases of stroke in the U.S. each year [1-3]. Of those suffering a major stroke, one-third will recover, one-third will die and one-third will be permanently impaired. Of the 750,000 strokes about half are caused by an embolic clot amenable to intervention [4, 5]. Other applications for this novel affinity contrast agent in vascular territory procedures include acute coronary thrombosis (84,000 patients/year/U.S.), peripheral arterial thrombosis (72,000 patients), DVT (75,000 patients) and PE (38,000) [6]. All of these patients will benefit from this molecule. One other side benefit of this molecule will be elimination or significant reduction of continuous large volume contrast injection for easier visualization of the clot during these interventional procedures.

描述（由申请人提供）：Biopsy Sciences, LLC NIH SBIR 第一阶段资助申请使用“Clot-Paint”在 X 射线下实时可视化凝块，这是一种新型碘化蛋白质受体结合分子项目摘要/摘要有超过 750,000 个新病例美国每年都有中风发生。在遭受严重中风的人中，三分之一将康复，三分之一将死亡，三分之一将永久受损。在美国，治疗中风患者的社会费用每年超过 580 亿美元。目前的急性栓塞性中风治疗方案包括症状出现后 3 小时内静脉注射 TPA、中风发作后 6 小时内注射动脉 TPA 以及使用机械血栓切除术。 FDA 在症状出现后最多 6 小时甚至可能更长时间内批准了 MERCI L5 检索系统。其他凝块回收/消融设备（AngioJet、Latis 激光设备、EPAR 激光、Penumbra 系统、Neuoronet 圈套器）正在研究中，但尚未投入商用。由于再灌注速度快且出血风险较低，去除血栓是理想的治疗方法。我们相信，在干预过程中实时看到血栓的能力将有助于缩短血栓清除的时间，并扩大愿意参与治疗栓塞性中风的医生数量。仅裂解可能需要长达 3 小时才能溶解凝块，而凝块去除可在 30 分钟内完成。我们的长期目标是推出一种新型造影剂“Clot-Paint”，通过插入闭塞动脉的导管将其注射到凝块上。 Clot-Paint 通过蛋白质受体位点紧密粘附在动脉内血栓上，同时含有足够的碘分子，使凝块对 X 射线束不透明，并在荧光镜成像下长时间可见。这种新分子由凝块结合蛋白和碘化分子组成。这种新型造影剂将允许神经介入放射科医生或心脏病专家通过实时荧光镜成像来可视化凝块，从而允许将设备准确定位到凝块中，并在移除之前确认凝块成功捕获到设备中。此外，任何向下游迁移的凝块碎片都可以很容易地被识别和去除。与目前进行中风干预的医生对这种新型造影剂的讨论已经证实了这种新型造影剂具有很高的潜在临床实用性。公共健康相关性：Biopsy Sciences, LLC NIH SBIR 第一阶段资助申请使用“Clot-Paint”在 X 射线下实时观察血块，这是一种新型碘化蛋白受体结合分子项目叙述美国有超过 750,000 例新中风病例。每年[1-3]。在遭受严重中风的人中，三分之一将康复，三分之一将死亡，三分之一将永久受损。在 750,000 例中风中，大约一半是由易于干预的栓塞引起的 [4, 5]。这种新型亲和造影剂在血管区域手术中的其他应用包括急性冠状动脉血栓形成（84,000 名患者/年/美国）、外周动脉血栓形成（72,000 名患者）、DVT（75,000 名患者）和 PE（38,000 名患者）[6]。所有这些患者都将从该分子中受益。该分子的另一个副作用是消除或显着减少连续大容量造影剂注射，以便在这些介入手术期间更容易观察到凝块。