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 Tc-99m-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 Tc-99m using the chelator MAG(3), and were evaluated for binding to host and non-host bacteria in vitro and in a mouse infection model. Results: In vitro, each Tc-99m-phage bound to its host at least 4-fold higher than to non-host bacteria. For example, Tc-99m-E79 showed 10- to 20-fold greater binding to host Pseudomonas aeruginosa compared to non-host Escherichia coli and Salmonella enterica, and Tc-99m-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 Tc-99m-phages were administered intravenously. After a further 3 It, the tissues were counted. Liver accumulation was highest for Tc-99m-E79, averaging 39% compared to an average of 13% for the other Tc-99m-phages. Animals infected with host bacteria showed infected thigh/normal thigh ratios of 14.2 for Tc-99m-E79, 2.9 for Tc-99m-P22, 3.5 for Tc-99m-VD-13 and 2.1 for Tc-99m-phage 60. Conclusions: Although specific host binding was observed in vitro for each of these four Tc-99m-phages, only Tc-99m-E79 showed specificity for its host in an in vivo model. (C) 2008 Elsevier Inc. All rights reserved.