Investigation of four (99m)Tc-labeled bacteriophages for infection-specific imaging.
BACKGROUND
This study investigated radiolabeled bacteriophages for specific detection of infection through gamma imaging. Previously, a (99m)Tc-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 (99m)Tc 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 (99m)Tc-phage bound to its host at least 4-fold higher than to non-host bacteria. For example, (99m)Tc-E79 showed 10- to 20-fold greater binding to host Pseudomonas aeruginosa compared to non-host Escherichia coli and Salmonella enterica, and (99m)Tc-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 (99m)Tc-phages were administered intravenously. After a further 3 h, the tissues were counted. Liver accumulation was highest for (99m)Tc-E79, averaging 39% compared to an average of 13% for the other (99m)Tc-phages. Animals infected with host bacteria showed infected thigh/normal thigh ratios of 14.2 for (99m)Tc-E79, 2.9 for (99m)Tc-P22, 3.5 for (99m)Tc-VD-13 and 2.1 for (99m)Tc-phage 60.


CONCLUSIONS
Although specific host binding was observed in vitro for each of these four (99m)Tc-phages, only (99m)Tc-E79 showed specificity for its host in an in vivo model.
Rusckowski
Mary
M
Department of Radiology, University of Massachusetts Medical School, Worcester, MA 01655-0243, USA. mary.rusckowski@umassmed.edu
Gupta
Suresh
S
Liu
Guozheng
G
Dou
Shuping
S
Hnatowich
Donald J
DJ
D000818:Animals; D001419:Bacteria / Q000821:virology*; D001424:Bacterial Infections / Q000000981:diagnostic imaging*; D001435:Bacteriophages / Q000737:chemistry / Q000472:pathogenicity; D004195:Disease Models, Animal; D004926:Escherichia coli / Q000821:virology; D054884:Host-Pathogen Interactions; D007239:Infections / Q000000981:diagnostic imaging*; D007553:Isotope Labeling / Q000379:methods; D007711:Klebsiella pneumoniae / Q000821:virology; D008297:Male; D051379:Mice; D011550:Pseudomonas aeruginosa / Q000821:virology; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000737:chemistry / Q000493:pharmacokinetics; D019779:Salmonella enterica / Q000821:virology; D013670:Sodium Pertechnetate Tc 99m / Q000737:chemistry / Q000493:pharmacokinetics*; D013045:Species Specificity; D014018:Tissue Distribution
D019275:Radiopharmaceuticals; D013670:Sodium Pertechnetate Tc 99m