MP11-15 DEVELOPMENT OF A TARGETED GADOLINIUM CONTRAST FOR NONINVASIVE OF MAGNETIC RESONANCE (MR) IMAGING OF NON-MUSCLE INVASIVE BLADDER CANCER

INTRODUCTION AND OBJECTIVES: Development of methods to noninvasively detect bladder cancer and eliminate cystoscopy remains the golden ring of urology research. While muscle invasive cancer is relatively easily imaged with standard CT and MRI technology, the ability to image non-muscle invasive bladder cancer (NMIBC) in a noninvasive manner remains a challenge. We report our experience with a tumor-targeted gadolinium contrast agent for MR imaging NMIBC. METHODS: The peptide ligand (CSNRDARRC) has previously been reported as having strong specificity for urothelial cancer. The peptide linked to a FITC was tested against a panel of human and rodent malignant and benign urothelial cell lines and imaged fluorescently. The peptide ligand was then conjugated to Gadolinium-DOTA (Gd). The linked Gd-ligand was studied in vitro against urothelial cell lines and compared to a scrambled peptide linked to Gd and visualized with MRI. The linked Gd-ligandide ligand was delivered intravesically into a murine model of non-muscle invasive bladder cancer for 90 minutes and then washed clear with saline and then imaged with MR. This approach was repeated using a intravenous (IV)delivery and renal filtering into the bladder to image the surface cancer. Intravenous delivery was also used to image the same tumor growing in the subcutis of the mouse. RESULTS: The FITC-ligand reproducibly bound to the surface of the various cancer lines but no to the benign immortalized urothelial and nonurothelial cell lines increasing fluorescence in cells 2.5-fold. The ligand-linked Gd was bound to the cancer cell growing in vitro increasing “MR signal” by 300% compared to scramble peptide-linked Gd. Intravesically delivered ligand-linked Gd successfully bound to the surface tumor and allowed for easy imaging for up to 6 hours after infusion. Similar results were found when the ligand-linked Gd was delivered intravenously and imaged 12e24 hour later. CONCLUSIONS: Cancer targeted Gd can be delivered intravesically and intravenously to allow for enhanced MR imaging of superficial bladder cancer. This approach may be first step toward MRbased noninvasive surveillance of the bladder for recurrent non-muscle invasive cancer.