Use of a MET-specific photoprobe to identify bladder tumors in an orthotopic xenograft model of bladder cancer.

Abstract

260 Background: Met over-expression has been found in bladder cancer (CaB). Stage and grade increases in urothelial carcinoma have been found to correlate with increases in Met expression. To assess whether molecular optical imaging could enhance the detection of bladder tumors, we used a Met-specific soluble photoprobe in an orthotopic xenograft model of bladder transitional cell carcinoma (TCC). Methods: An orthotopic xenograft murine model of CaB was developed with T24-Luciferase-positive bladder cancer cells. Presence of tumor was confirmed by luciferase optical imaging (Xenogen IVIS) of mice, 4 weeks after TCC cell implantation. Mice were euthanized and their bladders removed and bivalved. Bladders were incubated for 30 minutes with unbound fluorophore (Cy5**, Peak emission at 675 nM) and subsequently for another 30 minutes with Cy5** bound to a Met-specific peptide. Fluorescence imaging (Maestro) was performed before and after each incubation period. Following imaging, presence of tumor was confirmed histologically. Results: Cy5**-Met- peptide bound in sufficient density to tumor tissue in bladders for visualization by optical imaging. The tumor to normal bladder imaging ratio ranged from 2:1 to 8:1. Bladder regions with high uptake of Cy5**-Met-peptide corresponded to tumor areas confirmed by histological analysis. Conclusions: Cy5**-Met-peptide successfully targets Met in an orthotopic xenograft model of bladder cancer. Our results suggest that this agent maybe useful for the enhanced visualization of bladder cancer tumors during cystoscopy. No significant financial relationships to disclose.