title: Novel application of complementary imaging techniques to examine in vivo glucose metabolism in the kidney.
abstract: The metabolic status of the kidney is a determinant of injury susceptibility and a measure of progression for many disease processes; however, noninvasive modalities to assess kidney metabolism are lacking. In this study, we employed positron emission tomography (PET) and intravital multiphoton microscopy (MPM) to assess cortical and proximal tubule glucose tracer uptake, respectively, following experimental perturbations of kidney metabolism. Applying dynamic image acquisition PET with 2-18fluoro-2-deoxyglucose (18F-FDG) and tracer kinetic modeling, we found that an intracellular compartment in the cortex of the kidney could be distinguished from the blood and urine compartments in animals. Given emerging literature that the tumor suppressor protein p53 is an important regulator of cellular metabolism, we demonstrated that PET imaging was able to discern a threefold increase in cortical18F-FDG uptake following the pharmacological inhibition of p53 in animals. Intravital MPM with the fluorescent glucose analog 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxyglucose (2-NBDG) provided increased resolution and corroborated these findings at the level of the proximal tubule. Extending our observation of p53 inhibition on proximal tubule glucose tracer uptake, we demonstrated by intravital MPM that pharmacological inhibition of p53 diminishes mitochondrial potential difference. We provide additional evidence that inhibition of p53 alters key metabolic enzymes regulating glycolysis and increases intermediates of glycolysis. In summary, we provide evidence that PET is a valuable tool for examining kidney metabolism in preclinical and clinical studies, intravital MPM is a powerful adjunct to PET in preclinical studies of metabolism, and p53 inhibition alters basal kidney metabolism.
authors.affiliation: Division of Nephrology, Department of Medicine, Indiana University, Indianapolis, Indiana.
authors.forename: Takashi
authors.initials: T
authors.lastname: Hato
authors.affiliation: Division of Nephrology, Department of Medicine, Indiana University, Indianapolis, Indiana.
authors.forename: Allon N
authors.initials: AN
authors.lastname: Friedman
authors.affiliation: Division of Nephrology, Department of Medicine, Indiana University, Indianapolis, Indiana.
authors.forename: Henry
authors.initials: H
authors.lastname: Mang
authors.affiliation: Division of Nephrology, Department of Medicine, Indiana University, Indianapolis, Indiana.
authors.forename: Zoya
authors.initials: Z
authors.lastname: Plotkin
authors.affiliation: Division of Nephrology, Department of Medicine, Indiana University, Indianapolis, Indiana.
authors.forename: Shataakshi
authors.initials: S
authors.lastname: Dube
authors.affiliation: Department of Radiology and Imaging Sciences and the Indiana Institute for Biomedical Imaging Sciences, Indiana University, Indianapolis, Indiana.
authors.forename: Gary D
authors.initials: GD
authors.lastname: Hutchins
authors.affiliation: Department of Radiology and Imaging Sciences and the Indiana Institute for Biomedical Imaging Sciences, Indiana University, Indianapolis, Indiana.
authors.forename: Paul R
authors.initials: PR
authors.lastname: Territo
authors.affiliation: Department of Radiology and Imaging Sciences and the Indiana Institute for Biomedical Imaging Sciences, Indiana University, Indianapolis, Indiana.
authors.forename: Brian P
authors.initials: BP
authors.lastname: McCarthy
authors.affiliation: Department of Radiology and Imaging Sciences and the Indiana Institute for Biomedical Imaging Sciences, Indiana University, Indianapolis, Indiana.
authors.forename: Amanda A
authors.initials: AA
authors.lastname: Riley
authors.affiliation: Advanced Imaging Research Center, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas.
authors.forename: Kumar
authors.initials: K
authors.lastname: Pichumani
authors.affiliation: Advanced Imaging Research Center, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas.|Departments of Internal Medicine and Radiology, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas.|Veterans Affairs North Texas Health Care System, Dallas, Texas; and.
authors.forename: Craig R
authors.initials: CR
authors.lastname: Malloy
authors.affiliation: Department of Biochemistry and Molecular Biology, Indiana University, Indianapolis, Indiana.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Harris
authors.affiliation: Division of Nephrology, Department of Medicine, Indiana University, Indianapolis, Indiana.
authors.forename: Pierre C
authors.initials: PC
authors.lastname: Dagher
authors.affiliation: Division of Nephrology, Department of Medicine, Indiana University, Indianapolis, Indiana; tsutton2@iu.edu.
authors.forename: Timothy A
authors.initials: TA
authors.lastname: Sutton
mesh_terms: D000818:Animals; D003847:Deoxyglucose; D005462:Fluorine Radioisotopes; D005947:Glucose / Q000378:metabolism*; D007668:Kidney / Q000000981:diagnostic imaging* / Q000378:metabolism; D008297:Male; D051379:Mice; D036641:Microscopy, Fluorescence, Multiphoton / Q000379:methods*; D049268:Positron-Emission Tomography / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D005462:Fluorine Radioisotopes; D003847:Deoxyglucose; D005947:Glucose
keywords: kidney; multiphoton microscopy; p53; positron emission tomography