Preclinical Development and Validation of ASP5354: A Near-Infrared Fluorescent Agent for Intraoperative Ureter...

Area of Science:

• Surgical Innovation
• Medical Imaging
• Urology

Background:

• Iatrogenic ureteral injury (IUI) is a significant complication of abdominopelvic surgery, associated with high morbidity.
• Intraoperative ureteral visualization is crucial for reducing IUI incidence.
• Near-infrared fluorescence (NIRF) offers potential for real-time retroperitoneal visualization.

Purpose of the Study:

• To investigate the efficacy of an indocyanine green derivative, ASP5354, for intraoperative ureter visualization.
• To determine the optimal dose and duration of ureter visibility with ASP5354.
• To assess the safety profile of ASP5354 in preclinical models.

Main Methods:

• ASP5354 was administered intravenously to Wistar rats and Göttingen minipigs at varying doses.
• Ureter visualization was assessed in minipigs using a NIRF camera.
• Toxicological evaluation was performed in cynomolgus monkeys.

Main Results:

• 100% ureter visibility was achieved in minipigs at a dose of 0.01 mg/kg ASP5354, lasting up to 3 hours.
• The 0.01 mg/kg dose demonstrated no significant toxicity in cynomolgus monkeys.
• This dose is suggested as optimal for clinical use.

Conclusions:

• ASP5354 at 0.01 mg/kg provides effective ureter visualization for up to 3 hours.
• ASP5354 shows significant potential to reduce the risk of iatrogenic ureteral injury during abdominopelvic surgery.
• Further clinical investigation is warranted to confirm its utility in surgical settings.