B20

To enhance targeted molecular diagnostic efficacy and therapeutics, the carrier’s nonspecific interactions need to be minimal. Apart from the stability issues, easy conjugation chemistries and sensitive reporter detection system are essential. Here we exploited the high affinity between the neutravidin and biotin for in vivo near-infrared fluorescence imaging (NIRF imaging) of pancreas. Dyes that have a large stokes shift (LSS-Dye) (>80 nm) in the near infrared range was conjugated to neutravidin and utilized for targeted molecular imaging. Biotinylated exendin-4, a potent glucagons-like peptide 1 (GLP1) receptor antagonist was linked to the LSS conjugated neutravidin to target the GLP-1 rich pancreas. LSS dyes attached delivery system enabled maximal fluorescence signal while overcoming autofluorescence issues and minimizing nonspecific binding. NIRF imaging of the target positioned through various axial rotation angles obtained using a novel animal rotation stage further exemplifies the potential for LSS Dye-neutravidin scaffold as an efficient in vivo imaging agent. Apart from insulinomas, GLP-1 receptors are enriched in other tumors. Further, such a diagnostic and therapy monitoring system can be easily applied with emerging cancer biomarkers.

Third AACR International Conference on Molecular Diagnostics in Cancer Therapeutic Development-- Sep 22-25, 2008; Philadelphia, PA