Real-time, Near-Infrared Fluorescence Imaging with an Optimized Dye/Light Source/Camera Combination for Surgical Guidance of Prostate Cancer

Abstract

Purpose: The prostate-specific membrane antigen (PSMA) is a surface glycoprotein overexpressed on malignant prostate cells, as well as in the neovasculature of many tumors. Recent efforts to target PSMA for imaging prostate cancer rely on suitably functionalized low-molecular-weight agents. YC-27 is a low-molecular-weight, urea-based agent that enables near-infrared (NIR) imaging of PSMA in vivo. Experimental Design: We have developed and validated a laparoscopic imaging system (including an optimized light source, LumiNIR) that is capable of imaging small tumor burdens with minimal background fluorescence in real-time laparoscopic extirpative surgery of small prostate tumor xenografts in murine and porcine models. Results: In a mouse model, we demonstrate the feasibility of using real-time NIR laparoscopic imaging to detect and surgically remove PSMA-positive xenografts. We then validate the use of our laparoscopic real-time NIR imaging system in a large animal model. Our novel light source, which is optimized for YC-27, is capable of detecting as little as 12.4 pg/mL of the compound (2.48-pg YC-27 in 200-μL agarose). Finally, in a mouse xenograft model, we demonstrate that the use of real-time NIR imaging can reduce positive surgical margins (PSM). Conclusions: These data indicate that a NIR-emitting fluorophore targeted to PSMA may allow improved surgical treatment of human prostate cancer, reduce the rate of PSMs, and alleviate the need for adjuvant radiotherapy postoperatively. Clin Cancer Res; 21(4); 771–80. ©2014 AACR.

Theranostic Agents for Photodynamic Therapy of Prostate Cancer by Targeting Prostate-Specific Membrane Antigen

“…There remains an unmet clinical need to improve surgical techniques for identifying and removing cancerous tissue without damaging surrounding tissues during prostatectomy. Recently, Neuman and colleagues showed that the near-infrared (NIR) fluorescence probe YC-27 can improve the surgical treatment of prostate cancer and reduce the rate of positive surgical margins in real-time laparoscopic extirpative surgery (17).…”

PSMA-targeted contrast agents for intraoperative imaging of prostate cancer,

“…3–7 Despite the recent advancement in nuclear medicine-based therapy, surgical resection remains a definitive treatment for prostate cancer. 1,8 Compared to PSMA-targeted nuclear medicine, optical imaging could provide real-time guidance during prostate resection with highly sensitive, rapid, and non-radioactive NIR fluorescence light, and importantly, highlight areas of extracapsular extension or in-transit metastases. 7–9 However, surgery is performed without intraoperative image guidance because there are no clinically available optical contrast agents to help the surgeon ensure clean tumor margins and find small occult metastases in the surgical field.…”

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

“…Use of this probe in surgical resection has not been reported. More recently, Neuman et al reported the use of a low-molecular-weight NIR fluorescent agent (YC-27) that targets PSMA in preclinical models of prostate cancer (13, 35). Survival surgery in a mouse subcutaneous xenograft model comparing white light to real-time fluorescent was performed 20 hours post injection, with no recurrence in the fluorescent group (0/8).…”