The inability to visualize cancer during prostatectomy contributes to positive margins, cancer recurrence, and surgical side effects. A molecularly targeted fluorescent probe offers the potential for real-time intra-operative imaging.
The goal of this study was to develop a probe for image-guided prostate cancer surgery.
An antibody fragment (cys-diabody, cDb) against prostate stem cell antigen (PSCA) was conjugated to a far-red fluorophore, Cy5. The integrity and binding of the probe to PSCA was confirmed by gel electrophoresis, size exclusion and flow cytometry, respectively. Subcutaneous models of PSCA-expressing xenografts were used to assess the biodistribution and in vivo kinetics, while an invasive intramuscular model was utilized to explore the performance of Cy5-cDb-mediated fluorescence guidance in representative surgical scenarios. Finally, a prospective, randomized study comparing surgical resection with and without fluorescent guidance was performed to determine if this probe could reduce the incidence of positive margins.
Cy5-cDb demonstrated excellent purity, stability and specific binding to PSCA. In vivo imaging showed maximal signal-to-background ratios at 6 hours. In mice carrying PSCA+ and - dual xenografts, the mean fluorescence ratio of PSCA+/- tumors was 4. 4:1. In surgical resection experiments, residual tumors
Fluorescently labeled cDb enables real-time in vivo imaging of prostate cancer xenografts in mice, and facilitates more complete tumor removal than conventional white light surgery alone.
Clinical cancer research : an official journal of the American Association for Cancer Research. 2015 Oct 21 [Epub ahead of print]
Geoffrey A Sonn, Andrew S Behesnilian, Ziyue Karen Jiang, Kirstin A Zettlitz, Eric J Lepin, Laurent Bentolila, Scott M Knowles, Daniel J P Lawrence, Anna M Wu, Robert E Reiter
Urology, David Geffen School of Medicine at UCLA. , Urology, David Geffen School of Medicine at UCLA. , Urology, University of California. , Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA. , Crump Institute for Molecular Imaging, Molecular and Medical Pharmacology, UCLA. , Department of Chemistry and Biochemistry and California NanoSystems Institute, University of California. , Department of Pharmacology, UCLA. , Urology, David Geffen School of Medicine at UCLA. , Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA. , Dept of Urology, University of California, Los Angeles