PMID- 26832678 OWN - NLM STAT- MEDLINE DCOM- 20170926 LR - 20201209 IS - 1860-2002 (Electronic) IS - 1536-1632 (Linking) VI - 18 IP - 4 DP - 2016 Aug TI - Detection of Klebsiella. Pneumoniae Infection with an Antisense Oligomer Against its Ribosomal RNA. PG - 527-34 LID - 10.1007/s11307-015-0927-4 [doi] AB - PURPOSE: Previously, we demonstrated specific accumulation into bacteria of a 12-mer phosphorodiamidate morpholino (MORF) oligomer complementary to a ribosomal RNA (rRNA) segment found in all bacteria using the universal probe called Eub338 (Eub). Here, two MORF oligomers Eco and Kpn with sequences specific to the rRNA of Escherichia coli (Eco) and Klebsiella pneumoniae (Kpn) were investigated along with Eub and control (nonEub). PROCEDURES: To determine bacterial rRNA binding, oligomers were tagged with Alexa Fluor 633 (AF633) for fluorescence in situ hybridization (FISH) and fluorescence microscopy, and radiolabeled with technetium-99m (Tc-99m) for biodistribution and SPECT imaging in infected mice. RESULTS: By both FISH and fluorescence microscopy, Eub showed a positive signal in both E. coli and K. pneumoniae as expected, and Kpn showed significantly higher accumulation in K. pneumoniae with near background in E. coli (p < 0.01). Conversely, Eco was positive in both E. coli and K. pneumoniae, hence nonspecific. As determined by biodistribution, the accumulation of [(99m)Tc]Kpn was higher in the thigh infected with live K. pneumoniae than with live E. coli (p = 0.05), and significantly higher than with heat-killed K. pneumoniae (p = 0.02) in the target thigh. By SPECT imaging, the accumulation of [(99m)Tc]Kpn was obviously higher in its specific target of K. pneumoniae compared to an E. coli infected thigh. CONCLUSIONS: Kpn complementary to the rRNA of K. pneumoniae, labeled with Tc-99m or AF633, demonstrated specific binding to fixed and live K. pneumoniae in culture and in infected mice such that Tc-99m-labeled Kpn as the MORF oligomer may be useful for K. pneumoniae infection detection through imaging. FAU - Chen, Ling AU - Chen L AD - Division of Nuclear Medicine, Department of Radiology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA, 01655, USA. FAU - Cheng, Dengfeng AU - Cheng D AD - Department of Nuclear Medicine, Zhongshan Hospital, Fudan University, Shanghai, 200032, China. FAU - Liu, Guozheng AU - Liu G AD - Division of Nuclear Medicine, Department of Radiology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA, 01655, USA. FAU - Dou, Shuping AU - Dou S AD - Division of Nuclear Medicine, Department of Radiology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA, 01655, USA. FAU - Wang, Yuzhen AU - Wang Y AD - Division of Nuclear Medicine, Department of Radiology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA, 01655, USA. FAU - Liu, Xinrong AU - Liu X AD - ImmunoGen Inc, Waltham, MA, 02451, USA. FAU - Liu, Yuxia AU - Liu Y AD - Shanghai Institute of Applied Physics, Chinese Academy of Sciences, , Shanghai, 201800, China. FAU - Rusckowski, Mary AU - Rusckowski M AD - Division of Nuclear Medicine, Department of Radiology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA, 01655, USA. mary.rusckowski@umassmed.edu. LA - eng GR - R21 AI070857/AI/NIAID NIH HHS/United States PT - Journal Article PL - United States TA - Mol Imaging Biol JT - Molecular imaging and biology JID - 101125610 RN - 0 (Morpholinos) RN - 0 (Oligonucleotides, Antisense) RN - 0 (RNA, Ribosomal) RN - 0 (Radiopharmaceuticals) RN - 7440-26-8 (Technetium) SB - IM MH - Animals MH - In Situ Hybridization, Fluorescence MH - Klebsiella Infections/*diagnosis/diagnostic imaging/*microbiology/pathology MH - Klebsiella pneumoniae/*isolation & purification MH - Mice MH - Microscopy, Fluorescence MH - Morpholinos/pharmacology MH - Oligonucleotides, Antisense/*pharmacology MH - RNA, Ribosomal/*metabolism MH - Radiopharmaceuticals/metabolism MH - Technetium/metabolism MH - Tissue Distribution/drug effects MH - Tomography, Emission-Computed, Single-Photon MH - Tomography, X-Ray Computed OTO - NOTNLM OT - Antisense MORF OT - Bacterial infection imaging OT - Bacterial ribosomal RNA EDAT- 2016/02/03 06:00 MHDA- 2017/09/28 06:00 CRDT- 2016/02/03 06:00 PHST- 2016/02/03 06:00 [entrez] PHST- 2016/02/03 06:00 [pubmed] PHST- 2017/09/28 06:00 [medline] AID - 10.1007/s11307-015-0927-4 [pii] AID - 10.1007/s11307-015-0927-4 [doi] PST - ppublish SO - Mol Imaging Biol. 2016 Aug;18(4):527-34. doi: 10.1007/s11307-015-0927-4.