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Imaging bacterial infections with 2nd generation maltodextrins

使用第二代麦芽糊精对细菌感染进行成像

基本信息

批准号：
10417147
负责人：
Mark Myron Goodman
金额：
$ 66.77万
依托单位：
EMORY UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-08-15 至 2024-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10417147
关键词：
Abscess Acetals Animal Model Bacteria Bacterial Endocarditis Bacterial Infections Bacterial Model Chemical Structure Clinical Contrast Media Detection Diagnosis Early Diagnosis Endocarditis Environment Escherichia coli Evaluation Exhibits Family Generations Genus staphylococcus Gram-Negative Bacteria Gram-Negative Bacterial Infections Gram-Positive Bacteria Gram-Positive Bacterial Infections Health Healthcare Heart Valves Human Hydrolysis Image Imaging Techniques Imaging technology Implant In Vitro Infection Judgment Kinetics Label Lead Leukocytes Libraries Ligands Magnetic Resonance Imaging Mammalian Cell Metabolic Modeling Modification Morbidity - disease rate Osteomyelitis Positioning Attribute Positron-Emission Tomography Pre-Clinical Model Property Protocols documentation Pseudomonas aeruginosa Radiolabeled Rattus Resistance Scanning Sensitivity and Specificity Serum Specificity Staphylococcus aureus Streptococcus Structure Testing Translations Trioses base bone bone imaging clinically relevant cost experimental study imaging agent imaging probe in vivo maltodextrin mortality next generation novel scaffold targeted agent uptake

项目摘要

Bacterial infections ranging from heart valve infections (endocarditis) to bone infections (osteomyelitis) are a growing problem in health care today and cause significant morbidity and mortality. The unmet clinical need is our inability to diagnose bacterial infections at an early stage in a specific and sensitive manner. At present, heart valve infections, bone infections and abscesses are diagnosed on the basis of clinical judgment augmented by several non-specific imaging techniques (e.g., CT, MRI, white blood cell scans) and cultures. . However, these approaches are either indirect in the case of imaging or take several days in the case of cultures. The central objective of this proposal is to develop the next generation of maltodextrin based PET contrast agents that can image and diagnose early stage gram positive and gram negative infections. We have recently demonstrated that a new optimized maltodextrin targeting ligand termed thiomalto-triose that can image gram positive bacterial infections in vivo. The following specific aims are proposed: Specific Aim 1: Synthesis and Characterization of 18F thiomalto-triose based bacterial targeting ligands Specific Aim 2: Evaluation of lead compounds for the detection of gram negative infections in an animal model of bacterial osteomyelitis. Specific Aim 3: Evaluation of lead compounds for the detection of gram positive infections in an animal model of bacterial endocarditis

从心脏瓣膜感染(心内膜炎)到骨感染(骨髓炎)的细菌感染是一种这是当今卫生保健日益严重的问题，并导致严重的发病率和死亡率。未得到满足的临床需求是我们无法以特定和敏感的方式在早期阶段诊断细菌感染。目前，根据临床判断诊断心脏瓣膜感染、骨感染和脓肿。通过几种非特异性成像技术(例如，CT、MRI、白细胞扫描)和培养来增强。。然而，这些方法要么是间接的，要么在成像的情况下需要几天的时间文化。这项提议的中心目标是开发下一代基于麦芽糊精的PET 可以成像和诊断早期革兰氏阳性和革兰氏阴性感染的造影剂。我们最近证明了一种新的优化的麦芽糊精靶向配体硫代麦芽糖-三糖，它可以影像革兰氏阳性细菌感染活体。提出了以下具体目标：具体目标1：18F硫代麦芽三糖细菌靶向配体的合成与表征具体目标2：评价先导化合物在动物中检测革兰氏阴性感染的作用细菌性骨髓炎模型。具体目标3：评价先导化合物检测革兰氏阳性感染的效果细菌性心内膜炎动物模型的建立