A New PET Labeled Maltodextrin for Diagnosis of Bacterial Infections

用于诊断细菌感染的新型 PET 标记麦芽糖糊精

• 批准号: 9141215
• 负责人: Michael L Wach
• 金额: $ 22.5万
• 依托单位: MICROBIAL IMAGING, LLC
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-07-01 至 2017-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9141215
• 关键词: Animal Model; Antibiotics; Bacteria; Bacterial Infections; Businesses; Chemical Structure; Clinical; Contrast Media; Data; Debridement; Degenerative polyarthritis; Detection; Development; Diagnosis; Early Diagnosis; Elderly; Evaluation; Excision; Family; Fluorine; Generations; Glucose; Guidelines; Health Care Costs; Hip region structure; Image; Implant; Implantation procedure; Infection; Knee; Label; Laboratories; Lead; Life Expectancy; Maltose; Mammalian Cell; Marketing; Medical; Medical Device; Membrane; Microbial Biofilms; Modeling; Morbidity - disease rate; Muscle; Myocardium; Organ; Orthopedics; Pain; Pathway interactions; Patients; Phase I Clinical Trials; Positron; Positron-Emission Tomography; Preparation; Procedures; Property; Replacement Arthroplasty; Rodent Model; Safety; Savings; Sensitivity and Specificity; Source; Specificity; Staging; Technology; Testing; Time; Tissues; Toxic effect; Toxicology; Vendor; base; bone; design; fluorescence imaging; hip replacement arthroplasty; imaging agent; imaging modality; imaging probe; implantable device; in vivo; joint function; knee replacement arthroplasty; maltodextrin; medical implant; mortality; public health relevance; research study; single photon emission computed tomography; targeted imaging; treatment strategy

 DESCRIPTION (provided by applicant): We present a new family of contrast agents, based on targeting the maltodextrin transporter termed maltodextrin based imaging probes (MDPs), which are designed to image infections associated with implanted medical devices by fluorescent imaging. The chemical structure of an MDP is composed of maltodextrins conjugated to the positron emitting radioelement fluorine-18. MDPs have the potential to offer significant advantages over existing methods for imaging bacteria, such as FDG, as a result of their high specificity and sensitivity for bacteria. MDPs target the maltodextrin transport pathway and are internalized as a major source of glucose by bacteria. MDPs can therefore deliver millimolar concentrations of imaging probes into bacteria, making it possible to image low numbers of bacteria. MDPs also have high specificity for bacteria because mammalian cells do not express the maltodextrin transporter and thus cannot internalize contrast agents conjugated to maltose. Finally, MDPs are composed of glucose oligomers, which are hydrophilic and membrane impermeable. MDPs are therefore efficiently cleared from un-infected tissues in vivo, leading to low background in organs such as the heart and muscle, which should lead to high sensitivity imaging of implanted device infections. These unique properties allow MDPs to accurately image small numbers of bacteria in vivo. MDPs thus have the unique properties allow MDPs to accurately image small numbers of bacteria in vivo. MDPs thus have the potential to detect implant device infections at an early stage and enable their treatment before they are challenging to eradicate.

 描述（由申请人提供）：我们提出了一种新的造影剂系列，其基于靶向麦芽糊精转运蛋白，称为基于麦芽糊精的成像探针（MDP），旨在通过荧光成像对与植入式医疗器械相关的感染进行成像。MDP的化学结构由与正电子发射放射性元素氟-18共轭的麦芽糖糊精组成。MDP有可能提供显着的优势，超过现有的细菌成像方法，如FDG，由于其对细菌的高特异性和灵敏度。MDPs靶向麦芽糖糊精转运途径 并被细菌内化为葡萄糖的主要来源。因此，MDP可以将毫摩尔浓度的成像探针输送到细菌中，从而可以对少量细菌进行成像。MDP对细菌也具有高特异性，因为哺乳动物细胞不表达麦芽糖糊精转运蛋白，因此不能内化与麦芽糖缀合的造影剂。最后，MDP由葡萄糖低聚物组成，其是亲水性和膜不可渗透的。因此，MDP在体内从未感染的组织中有效清除，导致器官如心脏和肌肉中的低背景，这应该导致植入装置感染的高灵敏度成像。这些独特的特性使MDP能够准确地对体内少量细菌进行成像。因此，MDP具有独特的特性，允许MDP在体内准确地对少量细菌进行成像。因此，MDP有可能在早期阶段检测植入器械感染，并在难以根除之前进行治疗。