UNLABELLED: 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.
UNLABELLED: 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.
Authors: Filip Gemmel; Hans Van den Wyngaert; Charito Love; M M Welling; Paul Gemmel; Christopher J Palestro Journal: Eur J Nucl Med Mol Imaging Date: 2012-02-24 Impact factor: 9.236
Authors: Chetan Bettegowda; Catherine A Foss; Ian Cheong; Yuchuan Wang; Luis Diaz; Nishant Agrawal; James Fox; James Dick; Long H Dang; Shibin Zhou; Kenneth W Kinzler; Bert Vogelstein; Martin G Pomper Journal: Proc Natl Acad Sci U S A Date: 2005-01-14 Impact factor: 11.205
Authors: Xinghai Ning; Wonewoo Seo; Seungjun Lee; Kiyoko Takemiya; Mohammad Rafi; Xuli Feng; Daiana Weiss; Xiaojian Wang; Larry Williams; Vernon M Camp; Malveaux Eugene; W Robert Taylor; Mark Goodman; Niren Murthy Journal: Angew Chem Int Ed Engl Date: 2014-10-21 Impact factor: 15.336
Authors: Ling Chen; Yi Wang; Xinrong Liu; Shuping Dou; Guozheng Liu; Donald J Hnatowich; Mary Rusckowski Journal: Cancer Lett Date: 2008-08-23 Impact factor: 8.679