Synthesis of N₄'-[¹⁸F]fluoroalkylated ciprofloxacin as a potential bacterial infection imaging agent for PET study.
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.
Department of Nuclear Medicine, Cyclotron Research Center, Research Institute of Clinical Medicine, Chonbuk National University Medical School, Jeonju, Jeonbuk 561-712, Korea.
Kalme
K
Sachin
Eun-Mi
EM
Kim
Su-Jin
SJ
Cheong
Hwan-Jeong
HJ
Jeong
Seok Tae
ST
Lim
Myung-Hee
MH
Sohn
Dong Wook
DW
Kim
D000478:Alkylation; D000818:Animals; D001424:Bacterial Infections / Q000175:diagnosis / Q000382:microbiology; D001667:Binding, Competitive; D001692:Biological Transport; D002939:Ciprofloxacin / Q000031:analogs & derivatives / Q000097:blood / Q000138:chemical synthesis / Q000494:pharmacology; D027081:DNA Gyrase / Q000378:metabolism; D003952:Diagnostic Imaging / Q000379:methods*; D004355:Drug Stability; D004926:Escherichia coli / Q000187:drug effects / Q000254:growth & development; D005462:Fluorine Radioisotopes / Q000097:blood / Q000737:chemistry / Q000494:pharmacology; D054879:Halogenation; D006801:Humans; D007553:Isotope Labeling; D008826:Microbial Sensitivity Tests; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals / Q000097:blood / Q000138:chemical synthesis / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D059005:Topoisomerase II Inhibitors
D005462:Fluorine Radioisotopes; D019275:Radiopharmaceuticals; D059005:Topoisomerase II Inhibitors; D002939:Ciprofloxacin; D027081:DNA Gyrase