Synthesis of N₄′-[¹⁸F]Fluoroalkylated Ciprofloxacin as a Potential Bacterial Infection Imaging Agent for PET Study

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.

Investigation of 6-[18F]-Fluoromaltose as a Novel PET Tracer for Imaging Bacterial Infection

“…However these methods are not yet amenable to clinical translation. Clinically there have been several PET and SPECT tracers tested [1], [2], [4], [10]. The most promising of these was the study by Diaz et al using positron emission tomography (PET) and 1-2′-deoxy-2′-fluoro-β-D-arabinofuranosyl)-5-[ 124 I] iodouracil (FIAU), to identify bacterial lesions in patients with suspected musculoskeletal infections [11].…”

Bis‐tert‐Alcohol‐Functionalized Crown‐6‐Calix[4]arene: An Organic Promoter for Nucleophilic Fluorination

“…3-Fluoro-picoline-N-oxide was obtained from 3-chloro-picoline-N-oxide in 78 %y ield by using [b] Product Alkene 1 A1 21 00 86 12 2 [c] B12 [d] 100 28 16 3 [c] C31 00 89 2 4 [c] D31 00 19 81 5 [c] E41 00 59 23 6 [c] F31 00 80 www.chemeurj.org this method( Ta ble 3, entry 11)a nd the fluorinationo fasugar triflate proceeded at 80 8Cw ithin 1h,t op rovide the corresponding fluoro-sugar product in 96 %y ield (Table 3, entry 12). Af luoropropyl ciprofloxacin, [22] which has antibacteriala ctivity, was produced in 97 %yield by reactionwith the corresponding mesylatep recursor (Table 3, entry 13). Finally,c onsidering the importance of azadibenzocyclooctyne( ADIBO) derivatives in copper-free "click chemistry" for diversea pplications of fluorine-18 labeling chemistry, [23] af luorinated ADIBO derivative was prepared in 93 %y ield from the corresponding mesylate precursor by using our fluorination protocol (Table 3, entry 14).…”

Molecular Imaging: An Innovative Force in Musculoskeletal Radiology

“…There are numerous more recently developed technetium-labeled antibiotics, which include 99m Tc-alafosfalin and 99m Tc-cefuroxime axetil, many of which show promise but none of which has yet emerged as the desired sensitive and specific imaging agent [104]. Radiolabeling of antibiotics has extended beyond planar imaging to PET, with the development of agents such as N4F18-fluoroalkylated ciprofloxacin [105].…”