title: Biodistribution and pharmacokinetics of the (99m)Tc labeled human elastase inhibitor, elafin, in rats.
abstract: Elafin is a potent reversible inhibitor of the pro-inflammatory proteases leukocyte elastase and protease 3. It is currently in clinical development for the use in postoperative inflammatory diseases. We investigated the pharmacokinetics of (99m)Tc-labeled elafin ((99m)Tc-Elafin) in blood and individual organs in rat after bolus intravenous injection using the single photon emission tomography (SPECT). (99m)Tc-Elafin predominantly accumulated in the kidney reaching a maximum of 8.5% ± 0.1% of the injected dose per gram (ID/g) at 5 min post injection (p.i) and decreased only slowly during 24 h. In contrast, the initially high radio activity recorded in the other organs rapidly decreased parallel to the radioactivity detected in blood. The blood kinetics fits to a two compartment kinetics model. The radio activity in the dissected kidney was 4.98 ± 1.24%ID/g 24 h p.i, while in other organs, including the brain, no accumulation of (99m)Tc-Elafin was detected. At this time point 30% of the detected radioactivity in the kidney was identified to be not metabolized (99m)Tc-Elafin. In conclusion, the blood and organ-specific kinetic data provide a basis for planning of adequate dosing regimens and the high accumulation of intact elafin in the kidney favors clinical developments targeting inflammatory kidney diseases, such as chronic allograft nephropathy after kidney transplantation.
authors.affiliation: Department of Cardiovascular Surgery, University Hospital of Schleswig-Holstein (UK-SH), Campus Kiel, Arnold-Heller-Strasse 3, D-24105 Kiel, Germany.
authors.forename: Mark
authors.initials: M
authors.lastname: Kaschwich
authors.affiliation: Department of Nuclear Medicine, Molecular Imaging, Diagnostics and Therapy, University Hospital of Schleswig-Holstein (UK-SH), Campus Kiel, Karl Lennert Cancer Center North, Feldstrasse 21, D-24105, Germany.
authors.forename: Ulf
authors.initials: U
authors.lastname: Lützen
authors.affiliation: Department of Nuclear Medicine, Molecular Imaging, Diagnostics and Therapy, University Hospital of Schleswig-Holstein (UK-SH), Campus Kiel, Karl Lennert Cancer Center North, Feldstrasse 21, D-24105, Germany.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Nuclear Medicine, Molecular Imaging, Diagnostics and Therapy, University Hospital of Schleswig-Holstein (UK-SH), Campus Kiel, Karl Lennert Cancer Center North, Feldstrasse 21, D-24105, Germany.
authors.forename: Angelina
authors.initials: A
authors.lastname: Tjiong
authors.affiliation: Department of Nuclear Medicine, Molecular Imaging, Diagnostics and Therapy, University Hospital of Schleswig-Holstein (UK-SH), Campus Kiel, Karl Lennert Cancer Center North, Feldstrasse 21, D-24105, Germany.
authors.forename: Marlies
authors.initials: M
authors.lastname: Marx
authors.affiliation: Institute of Experimental and Clinical Pharmacology, University Hospital of Schleswig-Holstein (UK-SH), Campus Kiel, Arnold-Heller-Strasse 3, D-24105 Kiel, Germany.
authors.forename: Sierk
authors.initials: S
authors.lastname: Haenisch
authors.affiliation: Department of Dermatology, Venereology and Allergology, University Hospital of Schleswig-Holstein (UK-SH), Campus Kiel, Schittenhelmstrasse 7, D-24105 Kiel, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Wiedow
authors.affiliation: Department of General Pediatrics, University Hospital of Schleswig-Holstein (UK-SH), Campus Kiel, Arnold-Heller-Strasse 9, D-24105 Kiel, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Preuss
authors.affiliation: Institute of Experimental and Clinical Pharmacology, University Hospital of Schleswig-Holstein (UK-SH), Campus Kiel, Arnold-Heller-Strasse 3, D-24105 Kiel, Germany.
authors.forename: Juraj
authors.initials: J
authors.lastname: Culman
authors.affiliation: Department of Nuclear Medicine, Molecular Imaging, Diagnostics and Therapy, University Hospital of Schleswig-Holstein (UK-SH), Campus Kiel, Karl Lennert Cancer Center North, Feldstrasse 21, D-24105, Germany. Electronic address: mzuhayra@nuc-med.uni-kiel.de.
authors.forename: Maaz
authors.initials: M
authors.lastname: Zuhayra
mesh_terms: D000818:Animals; D053492:Elafin / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics*; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics*; D006801:Humans; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D013667:Technetium / Q000737:chemistry*; D014018:Tissue Distribution
chemical_list: D053492:Elafin; D004791:Enzyme Inhibitors; D013667:Technetium; D010196:Pancreatic Elastase
keywords: Elafin; Pharmacokinetic; Radiolabeling; SPECT; Tc-(99m)