Preserving Genital Nerve Function In Prostate Cancer: Imaging With A Molecular Imaging Agent

Proceedings: AACR 107th Annual Meeting 2016; April 16-20, 2016; New Orleans, LAPurpose: To establish proof-of-concept for the use of a molecular nerve imaging agent in demonstrating nerve tissue at risk during prostate surgery, and thus preventing iatrogenic sexual dysfunction. Erectile Dysfunction (ED) is a common complication of all forms of prostate cancer treatment, with incidence varying from 13-97% depending on the series quoted. There is broad agreement that treatment related damage to the neurovascular bundles is a root cause of the condition, with strong indications from many studies that preservation of the neurovascular bundles avoids post-treatment ED. The goal of this study is to use a novel neural imaging agent based on the non-toxic Tetanus Toxin C-fragment (TTc) to allow the visualization of the anatomy of the genital nerves, thus facilitating nerve-sparing therapies.Materials and methods: C57 Black male mice were anaesthetized (1-2% isofluorane/oxygen) and injected with 40 μg/10 μl of fluorescently labeled TTc790 in the tunica albuginea of the left corpus cavernosum. Animals were imaged live over a period of 3 hours post injection with a Xenogen IVIS 200 small animal imager. Animals were then euthanized, and the complete male reproductive system was surgically exposed and imaged ex-vivo with a Zeiss AxioZoom16 dissection microscope. The cavernosal nerves, prostatic tissue with intact nerve plexi were dissected and prepared for cryo-sectioning followed by fluorescent immuno-histology using standard methods.Results: En bloc excision of the prostate with the penis allowed imaging of the genital nerves using the retrograde transported neural marker, TTc790. We noted fluorescent TTc-related signal uptake along the expected course of the nerve tract ipsilateral to the injection site, and were able to clearly demonstrate the pelvic ganglion within the capsule of the prostate. Immuno-histological assessment with post cryo-sectioning confirmed our surgical microscopy findings, including our demonstration of the pelvic ganglion.Conclusions: We demonstrate the use of TTc790 as a nerve imaging agent for showing the anatomy of the cavernosal nerves and pelvic ganglion complex by intra-operative fluorescent imaging. This suggests that, with further work, image guidance could be provided to physicians and surgeons to spare these nerves during prostate carcinoma treatments, allowing the preservation of genital nerve function and improving quality of life in prostate cancer survivors.Citation Format: Lucia Le Roux, Daniela Ramos, Leo Flores, Dawid Schellingerhout. Preserving genital nerve function in prostate cancer: imaging with a molecular imaging agent. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1438.