Synthesis of N₄'-[¹⁸F]fluoroalkylated ciprofloxacin as a potential bacterial infection imaging agent for PET study

Bioconjug Chem. 2010 Dec 15;21(12):2282-8. doi: 10.1021/bc1002983. Epub 2010 Nov 4.

Abstract

Syntheses and evaluation of fluoroalkylated ciprofloxacin analogues are described. Among these analogues, N₄'-3-fluoropropylciprofloxacin (16) showed the most efficient antibacterial activity against E. coli strains (DH5α and TOP10) and a high binding affinity for DNA gyrase of bacteria. To develop bacteria-specific infection imaging agents for positron emission tomography (PET), no-carrier-added N₄-3-[¹⁸F]fluoropropylciprofloxacin ([¹⁸F]16) was prepared in two steps from N₄-3-methanesufonyloxypropylciprofloxacin, resulting in a 40% radiochemical yield (decay corrected for 100 min) via the tert-alcohol media radiofluorination protocol with high radiochemical purity (> 99%) as well as high specific activity (149 ± 75 GBq/μmol). The agent was stable (> 90%), as shown by an in vitro human serum stability assay. A bacterial uptake and blocking study of [¹⁸F]16 using authentic compound 16 in TOP10 cells demonstrated its high specific bacterial uptake. The results suggest that this radiotracer holds promise as a useful bacterial infection radiopharmaceutical for PET imaging.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkylation
  • Animals
  • Bacterial Infections / diagnosis
  • Bacterial Infections / microbiology
  • Binding, Competitive
  • Biological Transport
  • Ciprofloxacin* / analogs & derivatives
  • Ciprofloxacin* / blood
  • Ciprofloxacin* / chemical synthesis
  • Ciprofloxacin* / pharmacology
  • DNA Gyrase / metabolism
  • Diagnostic Imaging / methods*
  • Drug Stability
  • Escherichia coli / drug effects
  • Escherichia coli / growth & development
  • Fluorine Radioisotopes* / blood
  • Fluorine Radioisotopes* / chemistry
  • Fluorine Radioisotopes* / pharmacology
  • Halogenation
  • Humans
  • Isotope Labeling
  • Microbial Sensitivity Tests
  • Positron-Emission Tomography / methods*
  • Radiopharmaceuticals* / blood
  • Radiopharmaceuticals* / chemical synthesis
  • Radiopharmaceuticals* / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Topoisomerase II Inhibitors

Substances

  • Fluorine Radioisotopes
  • Radiopharmaceuticals
  • Topoisomerase II Inhibitors
  • Ciprofloxacin
  • DNA Gyrase