Synthesis of N4′-[18F]Fluoroalkylated Ciprofloxacin as a Potential Bacterial Infection Imaging Agent for PET Study
Synthesis of N4′-[18F]Fluoroalkylated Ciprofloxacin as a Potential Bacterial Infection Imaging Agent for PET Study
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DOI：
10.1021/bc1002983
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发表时间：
2010-12-01
影响因子：
4.7
通讯作者：
Kim, Dong Wook
中科院分区：
文献类型：
--
作者：
Sachin, Kalme;Kim, Eun-Mi;Kim, Dong Wook
介绍了氟烷基化环丙沙星类似物的合成与评价。其中N-4 ′-3-氟丙基环丙沙星（16）对大肠杆菌的抗菌活性最强。colt菌株（DH 5 α和TOP 10）和对细菌DNA旋转酶的高结合亲和力。为开发细菌特异性正电子发射断层显像剂，（[F-18]16）由N-4 ′-3-甲磺酰氧基丙基环丙沙星，导致40%的放射化学产率（衰变校正100分钟），具有高放射化学纯度（>99%）以及高比活度（149 +/-75 GBq/μ mol）。该试剂是稳定的（>90%），如通过体外人血清稳定性测定所示。在TOP10细胞中使用真实化合物16进行的[F-18]16的细菌摄取和阻断研究证明了其高特异性细菌摄取。结果表明，这种放射性示踪剂有望成为PET成像的有用的细菌感染放射性药物。
Syntheses and evaluation of fluoroalkylated ciprofloxacin analogues are described. Among these analogues, N-4'-3-fluoropropylciprofloxacin (16) showed the most efficient antibacterial activity against E. colt strains (DH5 alpha and TOP10) and a high binding affinity for DNA gyrase of bacteria. To develop bacteria-specific infection imaging agents for position emission tomography (PET), no-carrier-added N-4'-3-[F-18]fluoropropylciprofloxacin ([F-18]16) was prepared in two steps from N-4'-3-methanesufonyloxypropylciprofloxacin, resulting in a 40% radiochemical yield (decay corrected for 100 min) via the ten-alcohol media radiofluorination protocol with high radiochemical purity (>99%) as well as high specific activity (149 +/- 75 GBq/mu mol). The agent was stable (>90%), as shown by an in vitro human serum stability assay. A bacterial uptake and blocking study of [F-18]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.