title: (68) Ga-labeled Ciprofloxacin Conjugates as Radiotracers for Targeting Bacterial Infection.
abstract: With an aim of developing a bacteria-specific molecular imaging agent, ciprofloxacin has been modified with a propylamine spacer and linked to two common bifunctional chelators, p-SCN-Bz-DOTA and p-SCN-Bz-NOTA. The two ciprofloxacin conjugates, CP-PA-SCN-Bz-DOTA (1) and CP-PA-SCN-Bz-NOTA (2), were radiolabeled with (68)Ga in >90% radiochemical yield and were moderately stable in vitro for 4 h. The efficacy of (68)Ga-1 and (68)Ga-2 has been investigated in vitro in Staphylococcus aureus cells where bacterial binding of the radiotracers (0.9-1.0% for (68)Ga-1 and 1.6-2.3% for (68)Ga-2) could not be blocked in the presence of excess amount of unlabeled ciprofloxacin. However, uptake of radiotracers in live bacterial cells was significantly higher (p < 0.01) than that in non-viable bacterial cells. Bacterial infection targeting efficacy of (68)Ga-1 and (68)Ga-2 was tested in vivo in rats where the infected muscle-to-inflamed muscle ((68)Ga-1: 2 ± 0.2, (68)Ga-2: 3 ± 0.5) and infected muscle-to-normal muscle ratios ((68)Ga-1: 3 ± 0.4, (68)Ga-2: 6.6 ± 0.8) were found to improve at 120 min p.i. Fast blood clearance and renal excretion was observed for both the radiotracers. The two (68)Ga-labeled infection targeting radiotracers could discriminate between bacterial infection and inflammation in vivo and are worthy of further detailed investigation as infection imaging agents at the clinical level.
authors.affiliation: Radiopharmaceuticals Chemistry Section, Radiochemistry and Isotope Group, Bhabha Atomic Research Center, Mumbai, India.
authors.forename: Drishty
authors.initials: D
authors.lastname: Satpati
authors.affiliation: Board of Radiation and Isotope Technology, Navi Mumbai, India.
authors.forename: Chanda
authors.initials: C
authors.lastname: Arjun
authors.affiliation: Board of Radiation and Isotope Technology, Navi Mumbai, India.
authors.forename: Repaka
authors.initials: R
authors.lastname: Krishnamohan
authors.affiliation: Board of Radiation and Isotope Technology, Navi Mumbai, India.
authors.forename: Grace
authors.initials: G
authors.lastname: Samuel
authors.affiliation: Radiopharmaceuticals Chemistry Section, Radiochemistry and Isotope Group, Bhabha Atomic Research Center, Mumbai, India.
authors.forename: Sharmila
authors.initials: S
authors.lastname: Banerjee
mesh_terms: D000818:Animals; D001424:Bacterial Infections / Q000175:diagnosis*; D002939:Ciprofloxacin / Q000737:chemistry* / Q000493:pharmacokinetics; D005710:Gallium Radioisotopes / Q000737:chemistry*; D066244:Proton Magnetic Resonance Spectroscopy; D051381:Rats; D017208:Rats, Wistar; D021241:Spectrometry, Mass, Electrospray Ionization; D014018:Tissue Distribution
chemical_list: D005710:Gallium Radioisotopes; D002939:Ciprofloxacin
keywords: 68Ga; DOTA; NOTA; bacterial infection; ciprofloxacin