title: [18F]Ciprofloxacin, a new positron emission tomography tracer for noninvasive assessment of the tissue distribution and pharmacokinetics of ciprofloxacin in humans.
abstract: The biodistribution and pharmacokinetics of the fluorine-18-labeled fluoroquinolone antibiotic [(18)F]ciprofloxacin in tissue were studied noninvasively in humans by means of positron emission tomography (PET). Special attention was paid to characterizing the distribution of [(18)F]ciprofloxacin to select target tissues. Healthy volunteers (n = 12) were orally pretreated for 5 days with therapeutic doses of unlabeled ciprofloxacin. On day 6, subjects received a tracer dose (mean injected amount, 700 +/- 55 MBq, which contained about 0.6 mg of unlabeled ciprofloxacin) of [(18)F]ciprofloxacin as an intravenous bolus. Thereafter, PET imaging and venous blood sampling were initiated. Time-radioactivity curves were measured for liver, kidney, lung, heart, spleen, skeletal muscle, and brain tissues for up to 6 h after radiotracer administration. The first application of [(18)F]ciprofloxacin in humans has demonstrated the safety and utility of the newly developed radiotracer for pharmacokinetic PET imaging of the tissue ciprofloxacin distribution. Two different tissue compartments of radiotracer distribution could be identified. The first compartment including the kidney, heart, and spleen, from which the radiotracer was washed out relatively quickly (half-lives [t(1/2)s], 68, 57, and 106 min, respectively). The second compartment comprised liver, muscle, and lung tissue, which displayed prolonged radiotracer retention (t(1/2), >130 min). The highest concentrations of radioactivity were measured in the liver and kidney, the main organs of excretion (standardized uptake values [SUVs], 4.9 +/- 1.0 and 9.9 +/- 4.4, respectively). The brain radioactivity concentrations were very low (<1 kBq. g(-1)) and could therefore not be quantified. Transformation of SUVs into absolute concentrations (in micrograms per milliliter) allowed us to relate the concentrations at the target site to the susceptibilities of bacterial pathogens. In this way, the frequent use of ciprofloxacin for the treatment of a variety of infections could be corroborated.
authors.affiliation: Department of Clinical Pharmacology, Division of Clinical Pharmacokinetics, Medical University of Vienna, Allgemeines Krankenhaus, Währinger Gürtel 18-20, A-1090 Vienna, Austria. martin.brunner@meduniwien.ac.at
authors.forename: Martin
authors.initials: M
authors.lastname: Brunner
authors.forename: Oliver
authors.initials: O
authors.lastname: Langer
authors.forename: Georg
authors.initials: G
authors.lastname: Dobrozemsky
authors.forename: Ulrich
authors.initials: U
authors.lastname: Müller
authors.forename: Markus
authors.initials: M
authors.lastname: Zeitlinger
authors.forename: Markus
authors.initials: M
authors.lastname: Mitterhauser
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Wadsak
authors.forename: Robert
authors.initials: R
authors.lastname: Dudczak
authors.forename: Kurt
authors.initials: K
authors.lastname: Kletter
authors.forename: Markus
authors.initials: M
authors.lastname: Müller
mesh_terms: D000328:Adult; D000900:Anti-Bacterial Agents / Q000097:blood / Q000493:pharmacokinetics*; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism; D002939:Ciprofloxacin / Q000097:blood / Q000493:pharmacokinetics*; D005462:Fluorine Radioisotopes; D006207:Half-Life; D006801:Humans; D008297:Male; D049268:Positron-Emission Tomography; D011786:Quality Control; D019275:Radiopharmaceuticals / Q000097:blood / Q000493:pharmacokinetics*; D014018:Tissue Distribution
chemical_list: D000900:Anti-Bacterial Agents; D005462:Fluorine Radioisotopes; D019275:Radiopharmaceuticals; D002939:Ciprofloxacin