Pullambhatla Mrudula, Tessier Jean, Beck Graham, Jedynak Bruno, Wurthner Jens U, Pomper Martin G
Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University Macclesfield, UK.
Am J Nucl Med Mol Imaging. 2012;2(3):260-70. Epub 2012 Jul 10.
2'-Fluoro-2'-deoxy-1β-D-arabinofuranosyl-5-[(125)I]iodouracil ([(125)I]FIAU), a substrate for the thymidine kinase (TK) present in most bacteria, has been used as an imaging agent for single photon emission computed tomography (SPECT) in an experimental model of lung infection. Using SPECT-CT we show that [(125)I]FIAU is specific for bacterial infection rather than sterile inflammation. We report [(125)I]FIAU lung uptake values of 1.26 ± 0.20 percent injected dose per gram (%ID/g) in normal controls, 1.69 ± 0.32 %ID/g in lung inflammation and up to 7.14 ± 1.09 %ID/g in lung infection in ex vivo biodistribution studies at 24 h after intranasal administration of bacteria. Images of [(125)I]FIAU signal within lung can be used to estimate the number of bacteria present, with a limit of detection of 10(9) colony forming units per mL on the X-SPECT scanner. [(125)I]FIAU-Based bacterial imaging may be useful in preclinical models to facilitate the development of new antibiotics, particularly in cases where a corresponding human trial is planned.
2'-氟-2'-脱氧-1β-D-阿拉伯呋喃糖基-5-[(125)I]碘尿嘧啶([(125)I]FIAU)是大多数细菌中存在的胸苷激酶(TK)的底物,已被用作肺部感染实验模型中单光子发射计算机断层扫描(SPECT)的成像剂。使用SPECT-CT我们表明[(125)I]FIAU对细菌感染具有特异性,而非无菌性炎症。我们报告在鼻内接种细菌24小时后,[(125)I]FIAU在正常对照中的肺摄取值为每克注射剂量的1.26±0.20%(%ID/g),在肺部炎症中为1.69±0.32%ID/g,在肺部感染中高达7.14±1.09%ID/g。肺内[(125)I]FIAU信号图像可用于估计存在的细菌数量,在X-SPECT扫描仪上检测限为每毫升10(9)个菌落形成单位。基于[(125)I]FIAU的细菌成像在临床前模型中可能有助于新抗生素的开发,特别是在计划进行相应人体试验的情况下。