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：
10231244
负责人：
Mark Myron Goodman
金额：
$ 66.78万
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/10231244
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）的细菌感染是一个当今的医疗保健问题日益严重，并引起严重的发病率和死亡率。未满足的临床需求是我们无法以特定和敏感的方式在早期诊断细菌感染。现在，心脏瓣膜感染，骨骼感染和脓肿是根据临床判断诊断的通过几种非特异性成像技术（例如CT，MRI，白细胞扫描）和培养物增强。。但是，这些方法要么是在成像的情况下是间接的，要么在文化。该提案的核心目的是开发下一代基于麦芽糊精的宠物可以对比剂，可以对早期革兰氏正面和革兰氏阴性感染进行图像和诊断。我们最近证明了一种新的优化麦芽糊精的靶向配体称为Thiomalto-Triose，可以图像革兰氏阳性细菌感染体内。提出了以下具体目标：特定目标1：基于18f硫代三糖的合成和表征特定目的2：评估铅化合物检测动物中革兰氏阴性感染细菌骨髓炎的模型。特定目的3：评估铅化合物检测革兰氏阳性感染细菌心内膜炎的动物模型