Imaging bacterial infections with 2nd generation maltodextrins

从心脏瓣膜感染（心内膜炎）到骨骼感染（骨髓炎）的细菌感染是一种常见的疾病。 这是当今卫生保健中日益严重的问题，并导致显著的发病率和死亡率。未满足的临床需求是 我们无法在早期阶段以特定和敏感的方式诊断细菌感染。目前， 心脏瓣膜感染、骨感染和脓肿的诊断基于临床判断 通过几种非特异性成像技术（例如，CT、MRI、白色血细胞扫描）和培养。. 然而，这些方法在成像的情况下是间接的，或者在成像的情况下需要几天。 cultures.该提案的中心目标是开发下一代基于麦芽糊精的PET 造影剂可以成像和诊断早期革兰氏阳性和革兰氏阴性感染。我们 最近证明了一种新的优化的麦芽糖糊精靶向配体，称为硫代麦芽三糖， 体内革兰氏阳性细菌感染成像。建议的具体目标如下： 具体目标1：基于18 F硫代麦芽三糖的细菌靶向配体的合成和表征 具体目标2：评价先导化合物用于检测动物革兰氏阴性菌感染 细菌性骨髓炎模型。 具体目标3：评价先导化合物用于检测革兰氏阳性菌感染， 细菌性心内膜炎动物模型

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