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

Introduction: This 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. Methods: This 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. Results: In 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. Conclusions: Although 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