Abstract: SA-PO050
Measuring Nephron Endowment by Positron Emission Tomography
Session Information
- Engineering-Based Approaches to Problems in Nephrology
November 09, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Bioengineering
- 300 Bioengineering
Authors
- Bennett, Kevin M., Washington University in St. Louis, St. Louis, Missouri, United States
- Reichert, David E., Washington University School of Medicine, St Louis, Missouri, United States
- Beeman, Scott, Washington University School of Medicine, St Louis, Missouri, United States
- Charlton, Jennifer R., University of Virginia, Charlottesville, Virginia, United States
- Shoghi, Kooresh I., Washington University School of Medicine, St Louis, Missouri, United States
- Baldelomar, Edwin, University of Hawaii at Manoa, Honolulu, Hawaii, United States
Background
Nephron loss is a primary feature of kidney disease. Recent MRI tools using cationic ferritin (CF) offer a unique view of nephron mass in the intact kidney in vivo. We propose a novel contrast agent (RadioCF) based on CF for positron emission tomography (PET). Because RadioCF is detected in trace (<100 ug) doses in humans, RadioCF-PET may enable rapid translation of nephron endowment as a clinical marker.
Methods
Cationic ferritin was filled with Cu-64 created by cyclotron. Radiochemical purity was assessed by radioTLC. 24 mice were anesthetized and administered intravenous injections of radioCF (n = 8), radioNF (uncationized native ferritin, n = 8), or Cu-64 alone (n=8). Mice were injected with 50-80 μCi of radioCF. In four animals of each cohort, a single 3D image series was acquired post-injection.
Results
RadioCF accumulated specifically in the cortical glomeruli, while radioNF and Cu-64 did not. Binding of radioCF was confirmed by phosphorimaging. RadioNF and Cu-64 did not bind. Dynamic imaging and timecourse from renal cortex showed continuous radioCF accumulation in cortex over 90 minutes compared to radioNF or CU-64. Selective accumulation of RadioCF in cortex was confirmed by biodistribution.
Conclusion
RadioCF is a new, translatable molecular imaging tool. Because it binds selectively to the glomerulus, RadioCF accumulation should directly reflect the number of perfused nephrons.
PET imaging in mice after RadioCF injection. RadioCF accumulated in the renal cortex ( a, RadioCF in red), while radioNF and Cu-64 do not (c,e). Binding of radioCF, blue, was confirmed by phosphorimaging (b). radioNF and Cu-64 were absent (d,f). Dynamic whole body imaging and timecourse from the renal cortex (G) showed continuous radioCF accumulation in cortex over 90 minutes compared to radioNF or CU-64.