99mTc-MORF oligomers specific for bacterial ribosomal RNA as potential specific infection imaging agents |
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Authors: | Ling Chen Yi Wang Dengfeng Cheng Xinrong Liu Shuping Dou Guozheng Liu Donald J Hnatowich Mary Rusckowski |
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Institution: | Division of Nuclear Medicine, Department of Radiology, University of Massachusetts Medical School, Worcester, MA 01655, United States |
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Abstract: | PurposeRadiolabeled oligomers complementary to the 16S rRNA in bacteria were investigated as bacterial infection imaging agents.Methods and resultsIdentical sequences with backbones phosphorodiamidate morpholino (MORF), peptide nucleic acid (PNA), and phosphorothioate DNA (PS-DNA) were 99mTc-labeled and evaluated for binding to bacterial RNA. MORF binding to RNA from Escherichia coli strains SM101 and K12 was 4- and 150-fold higher compared to PNA and PS-DNA, respectively. Subsequently MORF oligomer in fluorescence in situ hybridization showed a stronger signal with study MORF compared to control in fixed preparations of two E. coli strains and Klebsiella pneumoniae. Flow cytometry analysis showed study MORF accumulation to be 8- and 80-fold higher compared to the control in live K. pneumoniae and Staphylococcus aureus, respectively. Further, fluorescence microscopy showed increased accumulation of study MORF over control in live E. coli and K. pneumonia. Binding of 99mTc-study MORF to RNA from E. coli SM101 and K12 was 30.4 and 117.8 pmol, respectively, per 1010 cells. Mice with K. pneumoniae live or heat-killed (sterile inflammation) in one thigh at 90 min for both 99mTc-study MORF and control showed higher accumulation in target thighs than in blood and all other organs expect for kidneys and small intestine. Accumulation of 99mTc-study MORF was significantly higher (p = 0.009) than that of the control in the thigh with sterile inflammation.ConclusionA 99mTc-MORF oligomer complimentary to the bacterial 16S rRNA demonstrated binding to bacterial RNA in vitro with specific accumulation into live bacteria. Radiolabeled MORF oligomers antisense to the bacterial rRNA may be useful to image bacterial infection. |
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Keywords: | MORF PNA PS-DNA Bacterial infection imaging SPECT/CT |
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