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dc.contributor.authorRusckowski, Mary
dc.contributor.authorGupta, Suresh
dc.contributor.authorLiu, Guozheng
dc.contributor.authorDou, Shuping
dc.contributor.authorHnatowich, Donald J.
dc.date2022-08-11T08:09:32.000
dc.date.accessioned2022-08-23T16:34:23Z
dc.date.available2022-08-23T16:34:23Z
dc.date.issued2004-07-06
dc.date.submitted2009-03-10
dc.identifier.citationJ Nucl Med. 2004 Jul;45(7):1201-8.
dc.identifier.issn0161-5505 (Print)
dc.identifier.pmid15235067
dc.identifier.urihttp://hdl.handle.net/20.500.14038/38317
dc.description.abstractBecause bacteriophages (phages) have a natural specificity for bacteria, it may be possible to develop radiolabeled phages as infection-specific agents. METHODS: The M13 phage was radiolabeled with (99m)Tc via mercaptoacetyltriglycine and purified by polyethylene glycol precipitation. After radiolabeling, the phage was tested for binding at 1, 5, and 10 min to Escherichia coli strain 2537, E. coli strain 25922, and Staphylococcus aureus strain 29213. The radiolabeled phage was also tested for specificity in mouse models that had received a subcutaneous injection of either live (infection/inflammation model) or heat-inactivated (inflammation model) cultures in a thigh. The labeled phage (10(9) plaque-forming units, 1-3.7 MBq) was administered either within 20 min (to minimize the contribution from inflammation) or 3 h after induction. The animals were killed 3 h later. RESULTS: The radiochemical purity of the labeled phage exceeded 95% by strip chromatography using instant thin-layer chromatography/acetone and paper/saline. Binding of the labeled phage to each of the 3 bacterial strains in vitro was immediate, reaching a maximum at 1 min. However, the percentage bound was significantly higher (P = 0.0008) for E. coli 2537 than for either of the other 2 bacteria (84% vs. 41% and 48%). Furthermore, binding to E. coli 2537 was unchanged at 10 min, whereas binding to both E. coli 25922 and S. aureus decreased to 33%. At 3 h in vivo, the ratio of target thigh to normal thigh was significantly higher (P < or = 0.017) in the infection/inflammation model (2 to 2.5 fold) than in the inflammation model (1.5 to 1.8) and therefore suggestive of increased accumulation specific to infection. The difference was slightly more pronounced in animals that received labeled phage at 20 min after inoculation, showing a ratio of 2.3 for infected thigh to normal thigh and a ratio of 1.6 for inflamed thigh to normal thigh. Although absolute uptake was lowest in the infection/inflammation thigh of mice infected with E. coli 2537, this finding was presumably due to the therapeutic effect of the phage on this strain. CONCLUSION: Radiolabeled bacteriophages should be further investigated as potential agents for specific imaging of infection.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=15235067&dopt=Abstract">Link to Article in PubMed</a>
dc.relation.urlhttp://jnm.snmjournals.org/content/45/7/1201.full.pdf+html
dc.subjectAnimals
dc.subjectBacteriophage M13
dc.subjectEscherichia coli Infections
dc.subjectIsotope Labeling
dc.subjectMetabolic Clearance Rate
dc.subjectMice
dc.subjectMyositis
dc.subjectRadiopharmaceuticals
dc.subjectTechnetium Tc 99m Mertiatide
dc.subjectTissue Distribution
dc.subjectLife Sciences
dc.subjectMedicine and Health Sciences
dc.titleInvestigations of a (99m)Tc-labeled bacteriophage as a potential infection-specific imaging agent
dc.typeJournal Article
dc.source.journaltitleJournal of nuclear medicine : official publication, Society of Nuclear Medicine
dc.source.volume45
dc.source.issue7
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/oapubs/1186
dc.identifier.contextkey770164
html.description.abstract<p>Because bacteriophages (phages) have a natural specificity for bacteria, it may be possible to develop radiolabeled phages as infection-specific agents. METHODS: The M13 phage was radiolabeled with (99m)Tc via mercaptoacetyltriglycine and purified by polyethylene glycol precipitation. After radiolabeling, the phage was tested for binding at 1, 5, and 10 min to Escherichia coli strain 2537, E. coli strain 25922, and Staphylococcus aureus strain 29213. The radiolabeled phage was also tested for specificity in mouse models that had received a subcutaneous injection of either live (infection/inflammation model) or heat-inactivated (inflammation model) cultures in a thigh. The labeled phage (10(9) plaque-forming units, 1-3.7 MBq) was administered either within 20 min (to minimize the contribution from inflammation) or 3 h after induction. The animals were killed 3 h later. RESULTS: The radiochemical purity of the labeled phage exceeded 95% by strip chromatography using instant thin-layer chromatography/acetone and paper/saline. Binding of the labeled phage to each of the 3 bacterial strains in vitro was immediate, reaching a maximum at 1 min. However, the percentage bound was significantly higher (P = 0.0008) for E. coli 2537 than for either of the other 2 bacteria (84% vs. 41% and 48%). Furthermore, binding to E. coli 2537 was unchanged at 10 min, whereas binding to both E. coli 25922 and S. aureus decreased to 33%. At 3 h in vivo, the ratio of target thigh to normal thigh was significantly higher (P < or = 0.017) in the infection/inflammation model (2 to 2.5 fold) than in the inflammation model (1.5 to 1.8) and therefore suggestive of increased accumulation specific to infection. The difference was slightly more pronounced in animals that received labeled phage at 20 min after inoculation, showing a ratio of 2.3 for infected thigh to normal thigh and a ratio of 1.6 for inflamed thigh to normal thigh. Although absolute uptake was lowest in the infection/inflammation thigh of mice infected with E. coli 2537, this finding was presumably due to the therapeutic effect of the phage on this strain. CONCLUSION: Radiolabeled bacteriophages should be further investigated as potential agents for specific imaging of infection.</p>
dc.identifier.submissionpathoapubs/1186
dc.contributor.departmentDepartment of Radiology, Division of Nuclear Medicine
dc.source.pages1201-8


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