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Real-time imaging with confocal laser endomicroscopy (CLE) probes that fit in standard endoscopes has emerged as a
clinically feasible technology for optical biopsy of bladder cancer. Confocal images of normal, inflammatory, and
neoplastic urothelium obtained with intravesical fluorescein can be differentiated by morphologic characteristics. We
compiled a confocal atlas of the urinary tract using these diagnostic criteria to be used in a prospective diagnostic
accuracy study. Patients scheduled to undergo transurethral resection of bladder tumor underwent white light cystoscopy
(WLC), followed by CLE, and histologic confirmation of resected tissue. Areas that appeared normal by WLC were
imaged and biopsied as controls. We imaged and prospectively analyzed 135 areas in 57 patients. We show that CLE
improves the diagnostic accuracy of WLC for diagnosing benign tissue, low and high grade cancer. Interobserver
studies showed a moderate level of agreement by urologists and nonclinical researchers. Despite morphologic
differences between inflammation and cancer, real-time differentiation can still be challenging. Identification of bladder
cancer-specific contrast agents could provide molecular specificity to CLE. By using fluorescently-labeled antibodies or
peptides that bind to proteins expressed in bladder cancer, we have identified putative molecular contrast agents for
targeted imaging with CLE. We describe one candidate agent - anti-CD47 - that was instilled into bladder specimens.
The tumor and normal urothelium were imaged with CLE, with increased fluorescent signal demonstrated in areas of
tumor compared to normal areas. Thus, cancer-specificity can be achieved using molecular contrast agents ex vivo in
conjunction with CLE.
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