Department of Nuclear Medicine, Cyclotron Research Center, Research Institute of Clinical Medicine, Chonbuk National University Medical School, Jeonju, Jeonbuk 561-712, Korea.
Bioconjug Chem. 2010 Dec 15;21(12):2282-8. doi: 10.1021/bc1002983. Epub 2010 Nov 4.
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.
描述了氟烷基化环丙沙星类似物的合成和评价。在这些类似物中，N₄'-3-氟丙基环丙沙星（16）对大肠杆菌菌株（DH5α 和 TOP10）表现出最有效的抗菌活性，并且对细菌的 DNA 回旋酶具有高结合亲和力。为了开发用于正电子发射断层扫描（PET）的细菌特异性感染成像剂，从 N₄-3-甲磺酰氧基丙基环丙沙星经两步制备了无载体添加的 N₄-3-[¹⁸F]氟丙基环丙沙星（[¹⁸F]16），采用叔醇介质放射性氟化方案，通过放射性化学产率为 40%（经 100 分钟衰变校正），放射化学纯度>99%，以及高比活度（149±75GBq/μmol）。通过体外人血清稳定性测定，该试剂具有稳定性（>90%）。使用真实化合物 16 在 TOP10 细胞中进行的[¹⁸F]16 细菌摄取和阻断研究表明，其具有高特异性细菌摄取。结果表明，该放射性示踪剂有望成为用于 PET 成像的有用的细菌感染放射性药物。
