title: Initial Preclinical Evaluation of 18F-Fluorodeoxysorbitol PET as a Novel Functional Renal Imaging Agent.
abstract: Accurate assessment of kidney function plays an essential role for optimal clinical decision making in a variety of diseases. The major intrinsic advantages of PET are superior spatial and temporal resolutions for quantitative tomographic renal imaging. 2-deoxy-2-18F-fluorodeoxysorbitol (18F-FDS) is an analog of sorbitol that is reported to be freely filtered at the renal glomerulus without reabsorption at the tubule. Furthermore, it can be synthesized via simple reduction of widely available18F-FDG. We tested the feasibility of18F-FDS renal PET imaging in rats.
  
  
  METHODS
  The systemic and renal distribution of18F-FDS were determined by dynamic 35-min PET imaging (15 frames × 8 s, 26 frames × 30 s, 20 frames × 60 s) with a dedicated small-animal PET system and postmortem tissue counting in healthy rats. Distribution of coinjected99mTc-diethylenetriaminepentaacetic acid (DTPA) was also estimated as a reference. Plasma binding and in vivo stability of18F-FDS were determined.
  
  
  RESULTS
  In vivo PET imaging visualized rapid excretion of the administrated18F-FDS from both kidneys, with minimal tracer accumulation in other organs. Initial cortical tracer uptake followed by visualization of the collecting system could be observed with high contrast. Split-function renography curves were successfully obtained in healthy rats (the time of maximal concentration [Tmax] right [R] = 2.8 ± 1.2 min, Tmaxleft [L] = 2.9 ± 1.5 min, the time of half maximal concentration [T1/2max] R = 8.8 ± 3.7 min, T1/2maxL = 11.1 ± 4.9 min). Postmortem tissue counting of18F-FDS confirmed the high kidney extraction (kidney activities at 10, 30, and 60 min after tracer injection [percentage injected dose per gram]: 1.8 ± 0.7, 1.2 ± 0.1, and 0.5 ± 0.2, respectively) in a degree comparable to99mTc-DTPA (2.5 ± 1.0, 1.5 ± 0.2, and 0.8 ± 0.3, respectively). Plasma protein binding of18F-FDS was low (<0.1%), and metabolic transformation was not detected in serum and urine.
  
  
  CONCLUSIONS
  In rat experiments,18F-FDS demonstrated high kidney extraction and excretion, low plasma protein binding, and high metabolic stability as preferable properties for renal imaging. These preliminary results warrant further confirmatory studies in large animal models and clinical studies as a novel functional renal imaging agent, given the advantages of PET technology and broad tracer availability.
authors.affiliation: Department of Nuclear Medicine, University of Würzburg, Würzburg, Germany.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Wakabayashi
authors.affiliation: Department of Nuclear Medicine, University of Würzburg, Würzburg, Germany Comprehensive Heart Failure Center, University of Würzburg, Würzburg, Germany; and.
authors.forename: Rudolf A
authors.initials: RA
authors.lastname: Werner
authors.affiliation: Department of Nuclear Medicine, University of Würzburg, Würzburg, Germany.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Hayakawa
authors.affiliation: Division of Nuclear Medicine and Molecular Imaging, The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, Maryland.
authors.forename: Mehrbod S
authors.initials: MS
authors.lastname: Javadi
authors.affiliation: Department of Nuclear Medicine, University of Würzburg, Würzburg, Germany Comprehensive Heart Failure Center, University of Würzburg, Würzburg, Germany; and.
authors.forename: Chen
authors.initials: C
authors.lastname: Xinyu
authors.affiliation: Department of Nuclear Medicine, University of Würzburg, Würzburg, Germany.
authors.forename: Ken
authors.initials: K
authors.lastname: Herrmann
authors.affiliation: Division of Nuclear Medicine and Molecular Imaging, The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, Maryland.
authors.forename: Steven P
authors.initials: SP
authors.lastname: Rowe
authors.affiliation: Department of Nuclear Medicine, University of Würzburg, Würzburg, Germany.
authors.forename: Constantin
authors.initials: C
authors.lastname: Lapa
authors.affiliation: Department of Nuclear Medicine, University of Würzburg, Würzburg, Germany Comprehensive Heart Failure Center, University of Würzburg, Würzburg, Germany; and thiguchi@ukw.de.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Higuchi
mesh_terms: D000818:Animals; D001798:Blood Proteins / Q000378:metabolism; D004355:Drug Stability; D007668:Kidney / Q000000981:diagnostic imaging* / Q000378:metabolism; D008297:Male; D049268:Positron-Emission Tomography / Q000379:methods*; D051381:Rats; D017208:Rats, Wistar; D013012:Sorbitol / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics; D014018:Tissue Distribution
chemical_list: C531573:2-deoxy-2-fluorosorbitol; D001798:Blood Proteins; D013012:Sorbitol
keywords: 18F-FDS; 99mTc-DTPA; PET; rat; renography