Translational imaging tools to nondestructively measure nephron mass

用于无损测量肾单位质量的平移成像工具

基本信息

批准号：
10325978
负责人：
Kevin M Bennett
金额：
$ 29.96万
依托单位：
XN BIOTECHNOLOGIES, LLC
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-07-01 至 2023-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10325978
关键词：
Activities of Daily Living Acute Renal Failure with Renal Papillary Necrosis Adult Affect Allografting Biodistribution Biological Assay Biological Markers Biopsy Biotechnology Blood Cations Chronic Kidney Failure Clinical Clinical Markers Collaborations Contrast Media Detection Development Diabetes Mellitus Diagnosis Diagnostic Dialysis procedure Disease Disease Marker Disease Progression Donor person Dose Early Diagnosis Early Intervention End stage renal failure Evaluation Ferritin Filtration Future Goals Health Human Hypertension Image Imaging Device Immune response Individual Injectable Investigational New Drug Application Kidney Kidney Diseases Kidney Transplantation Life Magnetic Resonance Imaging Mammals Maps Measurement Measures Mission Monitor Mus Nephrons Organ Organ Donor Outcome Pathway interactions Patient Monitoring Patients Phase Population Positron-Emission Tomography Predisposition Prevalence Procedures Production Proteins Radiation Dose Unit Radio Radioactive Radiolabeled Recombinants Renal function Risk Risk Factors Safety Screening procedure Small Business Technology Transfer Research Standardization Structure Technology Time Toxic effect Toxicology Tracer Transplantation Universities Variant Washington Work analog biomaterial compatibility clinical translation commercial application disease diagnosis dosimetry efficacy testing graft function immunogenicity improved improved outcome in vivo novel novel diagnostics post-transplant preclinical study radiotracer safety testing tool uptake urinary

项目摘要

PROJECT SUMMARY This work is aimed to improve outcomes in patients with kidney disease through improved diagnostics. Nephron mass is a measure of the functional capacity of the kidney. Its measurement could be transformative in detecting susceptibility to and progression of kidney diseases. However, no clinical tools or assays currently exist to directly measure nephron mass. We have developed tools using a novel targeted contrast agent (RadioCF) to directly measure nephron mass using positron emission tomography (PET). This technology, RadioCF-PET, has the potential to provide a more accurate assessment of kidney health and aid clinical decisions for patient treatment. RadioCF-PET also has the potential to be used in the assessment and allocation of renal transplants. This proposal will establish the feasibility of RadioCF-PET to measure nephron mass using a human recombinant form of RadioCF (HrRadioCF) to minimize toxicity, control synthesis and demonstrate the potential of this technology for clinical use. We will measure nephron mass in mice in vivo using RadioCF-PET with human recombinant RadioCF. We will perform initial toxicity studies with HrRadioCF to establish the safety of this radiotracer in mice that will inform the safety and efficacy testing in a Phase II proposal. In Phase II, we will perform extensive toxicity studies and characterization of the agent to support an exploratory investigational new drug application. Future application of RadioCF-PET will first focus on the evaluation of donor kidneys before transplant in both live and deceased donors to monitor allograft health during transit, and then will be adapted to monitor graft function after transplantation. Transplant evaluation provides a pathway to in-patient use of this technology as a new screening tool to monitor kidney health. This technology also has the potential to monitor patients at risk for kidney disease, such as patients with diabetes, indicating a large potential market for impact.

项目概要这项工作旨在通过改进诊断来改善肾脏疾病患者的治疗结果。肾单位质量是肾脏功能的衡量标准。它的测量可能具有变革性检测肾脏疾病的易感性和进展。然而，目前还没有临床工具或检测方法存在直接测量肾单位质量。我们开发了使用新型靶向造影剂的工具 (RadioCF) 使用正电子发射断层扫描 (PET) 直接测量肾单位质量。这项技术， RadioCF-PET，有潜力提供更准确的肾脏健康评估并帮助临床患者治疗的决定。 RadioCF-PET 也有潜力用于评估和肾移植的分配。该提案将确立 RadioCF-PET 测量肾单位的可行性使用人类重组形式的 RadioCF (HrRadioCF) 进行质量控制，以最大程度地减少毒性、控制合成和展示该技术的临床应用潜力。我们将测量小鼠体内肾单位的质量使用RadioCF-PET 和人类重组RadioCF。我们将使用 HrRadioCF 进行初步毒性研究确定这种放射性示踪剂在小鼠中的安全性，为第二阶段的安全性和有效性测试提供信息提议。在第二阶段，我们将进行广泛的毒性研究和药剂的表征，以支持探索性研究新药应用。 RadioCF-PET未来的应用将首先集中在在移植前对活体和已故捐赠者的捐赠肾脏进行评估，以监测同种异体移植物的健康状况在运输过程中，然后将适应移植后监测移植物功能。移植评估为住院患者使用该技术作为监测肾脏健康的新筛查工具提供了一条途径。这技术还有潜力监测有肾脏疾病风险的患者，例如糖尿病患者，表明影响力巨大的潜在市场。