Optical Imaging with Fluorescent Duplex DNAs

BackgroundOptical imaging, the use of fluorescence or bioluminescence,is a highly sensitive and noninvasive tool used to examine target tissues suchas tumors.  One advantage of usingoptical imaging over traditional radioactivity is that fluorescence can beturned on and off with the use of fluorescence resonance energy transfer(FRET).  Optical imaging techniquescould be used successfully in diagnosing surface lesions or in endoscopicprocedures.TechnologyUMass Medical School investigator Dr. Don Hnatowich andcolleagues have developed a FRET-based pretargeting technique using DNAoligomers (He et al (2007) Mol. Imaging Biol.9:17-23).  First, anantibody specific to the tumor or tissue of interest is conjugated to a DNAoligomer and is then administered. A second oligomer is then delivered, with a near-IR dye attached to thecomplimentary strand (F1) and a quencher dye on the other strand (F2).  Once this duplex reaches the targettissue, the oligomer conjugated to the antibody displaces the F2 strand. As aresult, fluorescence is only seen in the target tissue.Thistechnology may also be used for antisense targeting of mRNAs expressed only intissues of interest. In this scenario, the quencher is released only when thedye-labeled F1 strand binds the mRNA (Liu et al(2007) Bioconj. Chem. 18:1905-11).Competitive Advantages  Increasessignal to noise ratio for significantly better imaging Improvedsignal relative to radioactivity Fluorescencesignal can be turned on/off by FRET Near-infrareddyes can be detected at adequate depths for clinical imaging

United States

US Patent App. WO 2008/088865

USA