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. Public Health Relevance Statement PROJECT NARRATIVE Chronic kidney disease affects ~15% of the US population and the majority of patients are diagnosed too late to benefit from early intervention. This proposal will aid in the development of a new diagnostic tool for the kidney to enable early detection of diseases and to monitor overall kidney health.
Project Terms: Activities of Daily Living ; Activities of everyday life ; daily living functionality ; functional ability ; functional capacity ; Adult ; 21+ years old ; Adult Human ; adulthood ; Affect ; Biological Assay ; Assay ; Bioassay ; Biologic Assays ; Biopsy ; Biotechnology ; Biotech ; Blood ; Blood Reticuloendothelial System ; Cations ; Clinical Markers ; Contrast Media ; Contrast Agent ; Contrast Drugs ; Radiopaque Media ; Diabetes Mellitus ; diabetes ; Diagnosis ; Dialysis procedure ; Dialysis ; dialysis therapy ; Disease ; Disorder ; Donor person ; transplant donor ; Ferritin ; Filtration ; Filtration Fractionation ; Future ; Goals ; Health ; Human ; Modern Man ; Hypertension ; Vascular Hypertensive Disease ; Vascular Hypertensive Disorder ; high blood pressure ; hyperpiesia ; hyperpiesis ; hypertensive disease ; Kidney ; Kidney Urinary System ; renal ; Kidney Diseases ; Nephropathy ; Renal Disease ; kidney disorder ; renal disorder ; Chronic Kidney Failure ; Chronic Renal Disease ; Chronic Renal Failure ; chronic kidney disease ; Kidney Transplantation ; Kidney Grafting ; Kidney Transplants ; Renal Grafting ; Renal Transplantation ; Renal Transplants ; kidney tx ; Magnetic Resonance Imaging ; MR Imaging ; MR Tomography ; MRI ; Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance ; NMR Imaging ; NMR Tomography ; Nuclear Magnetic Resonance Imaging ; Zeugmatography ; Mammals ; Mammalia ; Maps ; Mission ; Mus ; Mice ; Mice Mammals ; Murine ; Nephrons ; Uriniferous Tube ; Organ Donor ; Patient Monitoring ; Patients ; Positron-Emission Tomography ; PET ; PET Scan ; PET imaging ; PETSCAN ; PETT ; Positron Emission Tomography Medical Imaging ; Positron Emission Tomography Scan ; Rad.-PET ; positron emission tomographic (PET) imaging ; positron emission tomographic imaging ; positron emitting tomography ; Production ; Proteins ; Risk ; Risk Factors ; Safety ; Standardization ; Technology ; Time ; Toxicology ; Transplantation ; transplant ; Universities ; Washington ; Work ; Measures ; Injectable ; Investigational New Drug Application ; Organ ; improved ; Procedures ; Clinical ; Phase ; Variant ; Variation ; Evaluation ; Predisposition ; Susceptibility ; Screening procedure ; screening tools ; Renal function ; kidney function ; Individual ; Measurement ; Disease Progression ; Early Intervention ; analog ; uptake ; Collaborations ; Immunological response ; host response ; immune system response ; immunoresponse ; Immune response ; tool ; Diagnostic ; Life ; Allografting ; Radiation Dose ; Radiation Dose Unit ; acute kidney injury ; Acute Renal Failure with Renal Papillary Necrosis ; biocompatibility ; biomaterial compatibility ; early detection ; Early Diagnosis ; radiolabel ; radiotracer ; dosimetry ; Toxicities ; Toxic effect ; Structure ; novel ; ESRD ; End-Stage Kidney Disease ; End-Stage Renal Disease ; End stage renal failure ; Radio ; Dose ; Detection ; Disease Marker ; Imaging Instrument ; Imaging Tool ; Imaging Device ; Radioactive ; Recombinants ; in vivo ; Small Business Technology Transfer Research ; STTR ; Monitor ; Tracer ; urinary ; Radiolabeled ; Development ; developmental ; Image ; imaging ; Pathway interactions ; pathway ; preclinical study ; pre-clinical study ; immunogenicity ; Biodistribution ; Outcome ; Population ; Prevalence ; novel diagnostics ; new diagnostics ; next generation diagnostics ; graft function ; commercial application ; Biological Markers ; bio-markers ; biologic marker ; biomarker ; safety testing ; efficacy testing ; disease diagnosis ; improved outcome ; clinical translation ; post-transplant ; post-transplantation ; posttransplant ; posttransplantation ;
