In vivo imaging of molecularly targeted phage

Kimberly A. Kelly, Peter Waterman and Ralph Weissleder

Year 2006, Volume 8, Issue 12

Abstract

Rapid identification of in vivo affinity ligands would have far reaching applications for imaging specific molecular targets, in vivo systems biology, and medical use. We have developed a high-throughput method for identifying and optimizing ligands to map and image biological targets of interest in vivo. We directly labeled viable phage clones with far red fluorochromes and comparatively imaged them in vivo by multichannel fluorescence ratio imaging. Using SPARC (osteonectin) and VCAM-1 as a model targets, we show that a) fluorescently labeled phage retain target specificity upon labeling, b) in vivo distribution can be quantitated (detection thresholds of ~300 phage/mm3 of tissue) throughout the entire depth of the tumor using fluorescent tomographic imaging, and c) that fluorescently labeled phage itself can serve as replenishable molecular imaging agents. The described method should find wide spread application in the rapid in vivo discovery and validation of affinity ligands and importantly, in using fluorochrome labeled phage clones as in vivo imaging agents.

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