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Investigation of four (99m)Tc-labeled bacteriophages for infection-specific imaging

Mary Rusckowski1, Suresh Gupta, Guozheng Liu

  • 1Department of Radiology, University of Massachusetts Medical School, Worcester, MA 01655-0243, USA. mary.rusckowski@umassmed.edu

Nuclear Medicine and Biology
|May 17, 2008
PubMed
Abstract

Insights

Radiolabeled bacteriophages show promise for infection detection. While in vitro tests confirmed host specificity for four phages, only technetium-99m-labeled E79 phage demonstrated effective in vivo targeting for diagnostic imaging.

Area of Science:

  • Biomedical imaging
  • Infectious disease diagnostics
  • Molecular imaging

Background:

  • Radiolabeled bacteriophages are being investigated for specific infection detection using gamma imaging.
  • Previous studies showed a (99m)Tc-labeled M13 phage specifically binds to Escherichia coli in vitro and in vivo.

Purpose of the Study:

  • To evaluate the in vitro and in vivo binding specificity of four radiolabeled bacteriophages (P22, E79, VD-13, and phage 60) for their respective bacterial hosts.
  • To determine if these radiolabeled phages can be used for gamma imaging detection of bacterial infections.

Main Methods:

  • Four bacteriophages (P22, E79, VD-13, phage 60) were radiolabeled with technetium-99m (99mTc) using the MAG(3) chelator.
  • In vitro binding assays were performed using host and non-host bacteria.
  • A mouse infection model was used, where mice were infected with bacteria, followed by intravenous administration of the radiolabeled phages. Tissue counts were measured after 3 hours.

Main Results:

  • All four (99m)Tc-labeled phages exhibited at least 4-fold higher binding to their specific hosts compared to non-host bacteria in vitro.
  • (99m)Tc-E79 showed 10- to 20-fold greater binding to Pseudomonas aeruginosa than to Escherichia coli or Salmonella enterica.
  • In vivo, (99m)Tc-E79 demonstrated the highest liver accumulation (39%) and the best infected thigh/normal thigh ratio (14.2) in mice infected with host bacteria.

Conclusions:

  • While all four tested (99m)Tc-phages showed specific host binding in vitro, only (99m)Tc-E79 demonstrated effective host specificity in an in vivo mouse model.
  • This suggests that (99m)Tc-E79 is a promising candidate for targeted gamma imaging of Pseudomonas aeruginosa infections.

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