An intravenous fluorophore for enhanced intraoperative nerve visualization

Iatrogenic nerve injury is a risk in many surgical procedures. We present our experience with a novel fluorescent agent to enhance the visualization of at-risk nerves during a prostatectomy in a canine model. Illuminare-1 is an intravenously administered myelin-binding fluorophore. After IRB approval and successfully visualizing target nerves in murine and porcine tests, we undertook a robotically-assisted prostatectomy on a dog, which has comparable genitourinary anatomy to a human. Dogs were positioned supine, anesthetized, the abdomen was insufflated, and the peri-prostatic and obturator nerves were exposed with a DaVinci SI Surgical System. A modified FDA-approved laparoscope with white and blue (370 – 425nm wave length) light settings was positioned via an assistant port to illuminate these nerves. A bolus of 1mg/kg of Illuminare-1 was administered intravenously with uninterrupted visualization of the presumed nerves. Fluorescent structures were resected for histological assessment. With 1mg/kg of Illuminare-1, nerves rapidly fluoresced under blue light, displaying a distinct hue. Fluorescence was seen within 90 seconds of administration and sustained for over three hours in the obturator and smaller periprostatic nerves. Tiny linear structures that were not initially seen under white light conditions were clearly identified as fluorescent tissue after injection with Illuminare-1. Seven fluorescent peri-prostatic structures were resected and all were histologically confirmed to be myelinated nerves. The cross-sectional nerve fiber diameters ranged from 64 – 247nm. Illuminare-1 enhanced the visualization of the neurovascular bundle in a dog. Phase-1 in-human trials with Illuminare-1 will follow to address the unmet need to reduce unintended surgical morbidity.