The translational utility would be to determine intra-operatively if there is extra-capsular prostatic cancer growth and potentially minimize positive surgical margins. The group previously reported in vitro animal studies with fluorescein bound to PSMA antibody that demonstrated prostatic specific illumination. They sought to increase the fluorescent intensity by increasing the concentration of fluorescein bound to each ligand. To do this, a novel fluorescent polymeric micelle probe was developed by encapsulating fluorescence molecules. These had a higher self-quenching concentration threshold within a micelle core. Folic acid or prostate-specific membrane antigen (PSMA) inhibitor analog molecules were conjugated on the surface of micelle. Fresh prostate tissue samples after robotic radical prostatectomy were obtained using a biopsy gun. Tissue samples were incubated with fluorescent polymeric micelle probe for 30 minutes, washed, and then imaged under a fluorescence microscope.
They estimated the ligand to dye ratio within each micelle at 1:10,000. The higher self-quenching concentration threshold of the dye molecules resulted in greater brightness compared to the conventional dye labeled antibody. Prostate tissues labeled with fluorescent polymeric micelles demonstrated corresponding fluorescence intensity 5-fold greater than tissue autofluorescence. Peripheral zone tissue had 20% additional fluorescence intensity compared to median lobe tissue. Systematic blocking experiments were performed to demonstrate tissue specific properties of the folic acid/PSMA inhibitor conjugated fluorescent micelles. Up to 40% decrease of fluorescence intensity was observed when the tissues were pre-treated with a high concentration of free folic acid or PSMA inhibitor.
Next they will perform in vivo studies to assess toxicity and effectiveness.
Presented by William K Johnston III, et al. at the American Urological Association (AUA) Annual Meeting - May 14 - 19, 2011 - Walter E. Washington Convention Center, Washington, DC USA
Reported for UroToday by Christopher P. Evans, MD, FACS, Professor and Chairman, Department of Urology, University of California, Davis, School of Medicine.
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