Fluorescent Image-Guided Surgery with an Anti-Prostate Stem Cell Antigen (PSCA) Diabody Enables Targeted Resection of Mouse Prostate Cancer Xenografts in Real-Time

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  



Newsletter subscription

Free Daily and Weekly newsletters offered by content of interest

The fields of GU Oncology and Urology are rapidly advancing. Sign up today for articles, videos, conference highlights and abstracts from peer-review publications by disease and condition delivered to your inbox and read on the go.