Imaging bacterial infections with radiolabeled 1-(2′-deoxy-2′-fluoro-β-D-arabinofuranosyl)-5-iodouracil

被引:102
作者
Bettegowda, C
Foss, CA
Cheong, I
Wang, YC
Diaz, L
Agrawal, N
Fox, J
Dick, J
Dang, LH
Zhou, SB
Kinzler, KW
Vogelstein, B
Pomper, MG [1 ]
机构
[1] Johns Hopkins Med Inst, Dept Radiol, Baltimore, MD 21231 USA
[2] Johns Hopkins Med Inst, Dept Otolaryngol Head & Neck Surg, Baltimore, MD 21231 USA
[3] Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21231 USA
[4] Johns Hopkins Med Inst, Howard Hughes Med Inst, Baltimore, MD 21231 USA
[5] Johns Hopkins Med Inst, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21231 USA
关键词
nuclear medicine; nucleoside analogs; single-photon emission computed tomography; thymidine kinase;
D O I
10.1073/pnas.0408861102
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Bacterial infections provide diagnostic dilemmas that could be enlightened by modern imaging technologies. We have developed a simple method for imaging bacterial infections in mice that relies on the phosphorylation and trapping of the thymidine kinase (TK) substrate 1-(2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl)-5-[I-125] iodouracil ([I-125]FIAU) within bacteria. FIAU was found to inhibit the growth of WT Escherichia coli but not a TK- strain, indicating that WT E coli could metabolize this compound. In silico analyses demonstrated that all pathogenic strains of bacteria whose genomes have been sequenced contain a TK gene highly homologous to the, E. coli TK. Accordingly, we demonstrated that localized infections caused by representatives of five genera of bacteria could be readily imaged with [I-125]FIAU. Such imaging provides a general method for the diagnosis of localized bacterial infections that could be translatable to the clinic.
引用
收藏
页码:1145 / 1150
页数:6
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