Rationally Designed, Target-specific Imaging Probes for Nephro-urology Diagnoses

用于肾泌尿科诊断的合理设计、针对特定目标的成像探头

• 批准号: 10659440
• 负责人: Jing Jin
• 金额: $ 57.72万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-04-15 至 2027-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10659440
• 关键词: Acute; Address; Autoimmunity; Basement membrane; Binding; Biopsy; Blood; Cells; Chimeric Proteins; Chronic; Chronic Phase; Circulation; Clinic; Clinical; Dangerousness; Data; Defect; Detection; Diagnosis; Diagnostic; Disease; Disease model; Early Diagnosis; Electrolytes; Excretory function; Extravasation; Filtration; Functional disorder; Glomerulonephritis; Goals; Human; Hybrids; Hypertension; IgG1; Image; Imaging Techniques; Impairment; Individual; Investigation; Ischemia; Kidney; Kidney Diseases; Lead; Ligands; Liquid substance; Longitudinal Studies; Maps; Masks; Measurement; Measures; Metabolic; Molecular; Nephrology; Nephrons; Onset of illness; Organ; Outcome; Pathologic; Pathology; Patient Care; Plasma Proteins; Pre-Clinical Model; Procedures; Process; Protein Engineering; Protein Sortings; Proteins; Proteinuria; Radioisotopes; Radionuclide Imaging; Recombinants; Renal function; Renal glomerular disease; Reperfusion Injury; Research; Resolution; Resources; Rodent Model; Route; Sclerosis; Secondary to; Series; Sorting; Specificity; Structure; System; Techniques; Technology; Testing; Time; Tracer; Translations; Tubular formation; Urine; Urology; VEGFA gene; Work; blood filtration; collaborative environment; density; design; functional decline; glomerular filtration; glomerulosclerosis; imaging agent; imaging approach; imaging probe; innovation; insight; kidney biopsy; kidney cortex; minimally invasive; mouse model; neonatal Fc receptor; nephrotoxicity; novel; novel strategies; personalized diagnostics; rational design; receptor; reuptake; standard of care; targeted agent; tool; uptake; urinary; wasting

Project Title: Rationally Designed, Target-specific Imaging Probes for Nephro-urology Diagnoses Project Summary The project focuses on novel design and testing of kidney-specific probes for radionuclide renal imaging. Unlike existing standard-of-care tracers used in the clinic that rely on passive uptake and clearance mechanisms, our recombinant probes are based on targeted design for mapping kidney functions, including filtration at the glomerulus and protein sorting at the proximal tubule. This approach enables functional renal imaging with molecular specificity. We adapted a fusion strategy in designing the probes, in which we joined modular segments of selected plasma proteins to form new hybrid probes. These modular segments are the functional units that can individually interact with their cognate renal receptors. Accordingly, it is anticipated that each probe will follow a guided intrarenal passage and sequentially interactions with intended receptors. This novel approach holds promise, as demonstrated in proof-of-concept studies and will continue to be pursued, for measuring distinct functions of the kidney. We will accomplish our research goal via three interconnected and synergistic Specific Aims, which are designed for measuring critical aspects of the renal function and pathophysiology, including glomerular filtration and tubular reuptake (Aim 1), glomerular density (Aim 2), and the early pathological changes in the filtration barrier (Aim 3). The studies will be conducted in acute and chronic settings as appropriate using relevant kidney disease models such as ischemic/reperfusion injury, nephrotoxicity, hypertension and autoimmunity, which are representative of common renal diseases in humans. Overall, our new probes are intended for directly addressing the needs for early and specific markers of renal diseases. The imaging data from these probes will provide important mechanistic insights for advancing the technologies toward their ultimate translation to patient care.

项目名称：用于肾泌尿科诊断的合理设计、针对特定目标的成像探头 项目概要 该项目的重点是放射性核素肾脏特异性探针的新颖设计和测试 成像。与临床中使用的现有标准护理示踪剂不同，这些示踪剂依赖于被动吸收和 清除机制，我们的重组探针基于用于绘制肾脏图谱的靶向设计 功能，包括肾小球的过滤和近端肾小管的蛋白质分选。这种做法 实现具有分子特异性的功能性肾脏成像。我们在设计时采用了融合策略 探针，其中我们将选定的血浆蛋白的模块化片段连接起来形成新的混合探针。 这些模块化部分是可以单独与其同源肾相互作用的功能单元。 受体。因此，预计每个探针将遵循引导的肾内通道并且 与预期受体的顺序相互作用。这种新颖的方法很有希望，如 概念验证研究并将继续进行，以测量肾脏的不同功能。我们 将通过三个相互关联和协同的具体目标来实现我们的研究目标，它们是 设计用于测量肾功能和病理生理学的关键方面，包括肾小球 滤过和肾小管再摄取（目标 1）、肾小球密度（目标 2）以及早期病理变化 过滤屏障（目标 3）。研究将酌情在急性和慢性环境中进行 使用相关的肾脏疾病模型，如缺血/再灌注损伤、肾毒性、高血压 和自身免疫，它们是人类常见肾脏疾病的代表。总的来说，我们的新探针 旨在直接满足肾脏疾病早期和特异性标志物的需求。成像 来自这些探测器的数据将为推动技术发展提供重要的机制见解 他们最终转化为患者护理。