Abstract 3919: A preclinical model of laparoscopy demonstrating the feasibility of detecting PSMA positive cells with a NIR fluorophore (YC-27): implications for strategies to decrease positive margins during prostatectomy.
Authors: Neuman Brian P. , Eifler John B. , Castanares Mark , Chowdhury Wasim H. , Chen Ying , Pomper Martin G. , Rodriguez Ronald 
Published: August 2014

Introduction:

Depending on the stage there is approximately a 4-54% positive surgical margin (+SM) following prostatectomy. Patients with +SM face the associated expense and impaired functional outcomes of salvage radiotherapy. To circumvent this, a low-molecular weight urea-based near infrared (NIR) fluorophore (YC-27) was developed to target the prostate specific membrane antigen (PSMA) for use in intraoperative imaging. PSMA is a transmembrane protein expressed in normal prostate and upregulated in cancer. PSMA expression correlates with Gleason score, advanced stage and PSA. We optimized dosing and timing in a small animal model for laparoscopic resection of PSMA positive tumors. Secondly, we demonstrate the feasibility of applying such a system in a porcine model.

Methods:

PSMA positive and negative tumors were established contralaterally on the flank of athymic male nude mice. YC-27 was administered intravenously at varying doses (9.5, 19.1, 39.7 [ug/Kg]) and sequentially imaged using a custom built laparoscopic system to obtain probe kinetics (1, 2, 3, 4, 6, 8, 10, 24 hrs post IV injection). Arbitrary pixel count was used to evaluate dosing and timing for signal to noise ratio. NIR guided laparoscopic resection was performed on mice with established PSMA positive and negative tumors 6 hrs post injection of 39.7 ug/Kg YC-27. In a porcine model, prestained human xenografts generated in a murine host were implanted behind the peritoneum of the abdominal cavity, and exploratory NIR laparoscopy was performed. In a porcine model, the kidney was observed with our laparoscopic NIR system after intravenous YC-27 administration.

Results:

In a murine model, the highest signal to noise ratio was determined to occur 6 hrs after injecting 39.7 ug/Kg YC-27. Using these parameters, NIR guided laparoscopic surgery facilitated full resection of the xenograft. In a porcine model, exploratory laparoscopy with our NIR system allowed detection of a prestained tumor implanted behind the peritoneum. In another experiment, strong fluorescent signal was observed from the porcine kidney immediately after IV injection of YC-27 which may be attributed to specific binding to PSMA, renal clearance, or a combination of both.

Conclusions:

YC-27 allows intraoperative localization of PSMA in real time using a prototype NIR guided laparoscopic surgical system. Pilot studies in large animals demonstrated excellent potential for clinical translation.

Citation Format: Brian P. Neuman, John B. Eifler, Mark Castanares, Wasim H. Chowdhury, Ying Chen, Martin G. Pomper, Ronald Rodriguez. A preclinical model of laparoscopy demonstrating the feasibility of detecting PSMA positive cells with a NIR fluorophore (YC-27): implications for strategies to decrease positive margins during prostatectomy. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3919. doi:10.1158/1538-7445.AM2013-3919