(99m)Tc-MORF oligomers specific for bacterial ribosomal RNA as potential specific infection imaging agents
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Authors
Chen, LingWang, Yi
Cheng, Dengfeng
Liu, Xinrong
Dou, Shuping
Liu, Guozheng
Hnatowich, Donald J.
Rusckowski, Mary
UMass Chan Affiliations
Department of Radiology, Division of Nuclear MedicineDocument Type
Journal ArticlePublication Date
2013-11-01Keywords
AnimalsBacterial Infections
Escherichia coli
Half-Life
In Situ Hybridization, Fluorescence
Klebsiella pneumoniae
Mice
Microscopy, Fluorescence
Morpholinos
Organotechnetium Compounds
RNA, Bacterial
RNA, Ribosomal, 16S
Radiopharmaceuticals
Staphylococcus aureus
Tissue Distribution
Tomography, Emission-Computed, Single-Photon
Tomography, X-Ray Computed
MORF
PNA
PS-DNA
bacterial infection imaging
SPECT/CT
Bacteria
Bacterial Infections and Mycoses
Medicinal and Pharmaceutical Chemistry
Medicinal-Pharmaceutical Chemistry
Radiology
Metadata
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PURPOSE: Radiolabeled oligomers complementary to the 16S rRNA in bacteria were investigated as bacterial infection imaging agents. METHODS AND RESULTS: Identical sequences with backbones phosphorodiamidate morpholino (MORF), peptide nucleic acid (PNA), and phosphorothioate DNA (PS-DNA) were (99m)Tc-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 (99m)Tc-study MORF to RNA from E. coli SM101 and K12 was 30.4 and 117.8pmol, respectively, per 10(10) cells. Mice with K. pneumoniae live or heat-killed (sterile inflammation) in one thigh at 90min for both (99m)Tc-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 (99m)Tc-study MORF was significantly higher (p = 0.009) than that of the control in the thigh with sterile inflammation. CONCLUSION: A (99m)Tc-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.Source
Bioorg Med Chem. 2013 Nov 1;21(21):6523-30. doi: 10.1016/j.bmc.2013.08.034. Link to article on publisher's siteDOI
10.1016/j.bmc.2013.08.034Permanent Link to this Item
http://hdl.handle.net/20.500.14038/48277PubMed ID
24054488Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1016/j.bmc.2013.08.034
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