Investigation of four 99mTc-labeled bacteriophages for infection-specific imaging

IntroductionThis study investigated radiolabeled bacteriophages for specific detection of infection through gamma imaging. Previously, a 99mTc-labeled M13 phage demonstrated specific binding for its host Escherichia coli in vitro and in mice through imaging.MethodsThis study was extended to phages P22, E79, VD-13 and phage 60. Each was radiolabeled with 99mTc using the chelator MAG3, and were evaluated for binding to host and non-host bacteria in vitro and in a mouse infection model.ResultsIn vitro, each 99mTc-phage bound to its host at least 4-fold higher than to non-host bacteria. For example, 99mTc-E79 showed 10- to 20-fold greater binding to host Pseudomonas aeruginosa compared to non-host Escherichia coli and Salmonella enterica, and 99mTc-phage 60 showed 20-fold greater binding to host Klebsiella pneumoniae over non-hosts. Mice received host or non-host bacteria in one thigh, and 3 h later, the 99mTc-phages were administered intravenously. After a further 3 h, the tissues were counted. Liver accumulation was highest for 99mTc-E79, averaging 39% compared to an average of 13% for the other 99mTc-phages. Animals infected with host bacteria showed infected thigh/normal thigh ratios of 14.2 for 99mTc-E79, 2.9 for 99mTc-P22, 3.5 for 99mTc-VD-13 and 2.1 for 99mTc-phage 60.ConclusionsAlthough specific host binding was observed in vitro for each of these four 99mTc-phages, only 99mTc-E79 showed specificity for its host in an in vivo model.