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

基本信息

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
项目类别：
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

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

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项目摘要

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：合理设计的，针对目标特定的成像探针，用于肾画学诊断项目摘要该项目着重于放射性核素肾脏的肾脏特异性探针的新设计和测试成像。与依靠被动吸收和诊所中使用的现有护理标准示踪剂不同清除机制，我们的重组探针基于用于映射肾脏的靶向设计功能，包括肾小球处的过滤和近端小管处的蛋白质排序。这种方法启用具有分子特异性的功能性肾脏成像。我们对设计融合策略进行了调整探针，我们在其中连接了选定的等离子体蛋白的模块化片段，形成了新的杂种探针。这些模块化段是可以单独与其同源肾脏相互作用的功能单元受体。因此，预计每个探针将遵循指导的肾内通过，并依次与预期的受体相互作用。这种小说的方法具有前途，如概念验证研究并将继续进行，以衡量肾脏的不同功能。我们将通过三个互连和协同特定目标来实现我们的研究目标设计用于测量肾功能和病理生理学的关键方面，包括肾小球过滤和管状再摄取（AIM 1），肾小球密度（AIM 2）以及早期的病理变化过滤屏障（AIM 3）。这些研究将适当地在急性和慢性环境中进行使用相关的肾脏疾病模型，例如缺血/再灌注损伤，肾毒性，高血压和自身免疫性，代表着人类常见的肾脏疾病。总体而言，我们的新探测旨在直接满足肾脏疾病的早期和特定标记的需求。成像来自这些探针的数据将提供重要的机理见解，以推进技术他们的最终转化为患者护理。