Development of MB-102 as fluorescent tracer for ocular angiography

开发MB-102作为眼血管造影荧光示踪剂

• 批准号: 9199037
• 负责人: Richard B Dorshow
• 金额: $ 18.15万
• 依托单位: MEDIBEACON, INC.
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-01 至 2018-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9199037
• 关键词: Adoption; Adverse reactions; Affect; Age related macular degeneration; Allergic Reaction; Anaphylaxis; Angiography; Animals; Anterior; Binding Proteins; Biocompatible; Blood; Canis familiaris; Cessation of life; Clinical Trials; Data; Detection; Development; Diabetic Retinopathy; Diagnosis; Diagnostic; Diagnostic Procedure; Disease; Disease Progression; Dose; Dyes; Eye; Fluorescein; Fluorescein Angiography; Fluorescence; Fluorescence Angiography; Fluorescent Dyes; Generations; Generic Drugs; Goals; Half-Life; Hour; Human; Hypertensive Retinopathy; Image; Imagery; Inflammation; Injection of therapeutic agent; Kidney; Lead; Marketing; Metabolism; Mus; Myocardial Infarction; Nausea and Vomiting; Pain; Patients; Pharmacologic Substance; Phase; Phase II Clinical Trials; Physicians; Physiological; Plasma; Procedures; Production; Property; Protocols documentation; Reaction; Reagent; Research Infrastructure; Retinal; Safety; Sales; Seizures; Site; Small Business Innovation Research Grant; Testing; Therapeutic procedure; Time; Toxicology; Tracer; Vascular Diseases; Veins; cohort; commercial application; commercialization; disease diagnosis; human disease; human study; improved; novel; pre-clinical; response; standard of care; tool

PROJECT SUMMARY/ABSTRACT Fluorescent angiography is a commonly used diagnostic tool for visualizing eye vasculature when a physician suspects a patient suffers from retinal vascular diseases such as diabetic retinopathy and age-related macular degeneration. To visualize eye vasculature, the fluorescent dye fluorescein is injected intravenously. Administration of fluorescein is associated with both mild and severe adverse reactions. Mild reactions such as nausea, vomiting, and pain at the injection site are frequent and likely associated with the need to dissolve fluorescein in alkaline solutions. More severe reactions, such as allergic reactions, seizures, and death are less frequent but limit ocular angiography use since a crash cart must be present during fluorescein administration. MediBeacon has developed a second-generation IV fluorescent dye (MB-102) with several advantages over fluorescein. MB-102 is soluble at physiological pH and therefore does not require alkaline dissolution. Also, there is no known metabolism of MB-102 in humans, suggesting that the likelihood of an anaphylactic response will be considerably lower than for fluorescein. We have preliminary proof of concept data from mice showing that MB-102 can be used to visualize ocular vasculature. MB-102 has undergone full preclinical toxicology and was found safe in a 32-subject Phase I human study for another indication. This SBIR will assess the use of MB-102 for visualizing ocular vasculature in healthy dogs and dogs with either hypertensive or diabetic retinopathy. The first specific aim of this project is to establish a standardized protocol for MB-102 administration and compare the quality of images obtained with MB-102 to images obtained using standard fluorescein angiography. As part of this aim we will first optimize the imaging setup for detection of MB-102 and then establish the optimal MB-102 dose for performing anterior and posterior segment angiography in healthy dogs. The second specific aim of this project tests MB-102 in dogs suffering from hypertensive or diabetic retinopathy. This aim is to compare and contrast the diagnostic capabilities of MB-102 to standard fluorescein imaging. The goal of this project is to prove that MB-102 can provide the same diagnostic information as fluorescein in eye vasculature diseases. According to our internal analysis, fluorescein is a $225 million annual market served by a number of generic pharmaceutical companies. A superior proprietary reagent with an improved safety profile and better diagnostic utility should lead to significant market adoption.

项目总结/摘要 荧光血管造影术是一种常用的诊断工具，用于可视化眼睛血管系统， 怀疑患者患有视网膜血管疾病，如糖尿病视网膜病变和老年性黄斑病变， 退化为了使眼睛血管可视化，荧光染料荧光素被静脉注射。 荧光素的给药与轻度和重度不良反应相关。轻度反应，如 恶心、呕吐和注射部位疼痛是常见的，可能与需要溶解 碱性溶液中的荧光素。更严重的反应，如过敏反应，癫痫发作和死亡较少 频繁但有限的眼部血管造影术的使用，因为在荧光素施用期间必须存在急救车。 MediBeacon开发了第二代IV荧光染料（MB-102），与 荧光素MB-102在生理pH值下可溶，因此不需要碱溶解。还有， MB-102在人体中没有已知的代谢，这表明过敏反应的可能性 响应将显著低于荧光素。我们有初步的概念验证数据从老鼠 显示MB-102可用于可视化眼部脉管系统。MB-102已经过完整的临床前试验 毒理学，并在32名受试者的I期人体研究中发现对另一种适应症是安全的。该SBIR将 评估MB-102在健康犬和高血压犬中用于眼血管可视化的用途 或糖尿病视网膜病变。该项目的第一个具体目标是为MB-102制定标准化协议 给药，并比较MB-102获得的图像质量与标准品获得的图像质量 荧光素血管造影作为这一目标的一部分，我们将首先优化MB-102检测的成像设置 然后确定MB-102进行前后段血管造影的最佳剂量， 健康的狗该项目的第二个具体目标是在患有高血压或高血压的犬中测试MB-102。 糖尿病视网膜病变目的是比较和对比MB-102与标准 荧光成像该项目的目标是证明MB-102可以提供相同的诊断 在眼血管疾病中的荧光素信息。根据我们的内部分析，荧光素是一个225美元 年销售量达1000万美元，由多家非专利制药公司提供服务。上级专利 具有改进的安全性和更好的诊断实用性的试剂将导致巨大的市场 领养