Abstract 2533: Image-guided surgery with a new optical probe for breast cancer

Abstract Accurate surgical removal of tumors significantly impacts patient outcomes. However, distinguishing between breast tumors and normal tissue during surgery is often challenging or even impossible. Given the lack of visual discrepancy between malignant and surrounding normal tissue, current breast-conserving surgery (BCS) is associated with a high re-excision rate. Due to this clinical challenge, a new method of complete tumor removal at the initial surgery is needed. To address this, we developed a new fluorescent imaging agent, ICG-p28, for intraoperative imaging guidance to better aid surgeons in achieving negative margins in BCS. ICG-p28 consists of the clinically nontoxic tumor-targeting peptide p28 and the FDA-approved near-infrared (NIR) dye indocyanine green. Here, we evaluated our imaging approach with ICG-p28 in vitro and in breast cancer animal models. First, we determined the detection limit of the objective size and depth using phantoms incorporating tumor-simulating inclusions. Even with the smallest objective (1 mm), NIR fluorescence imaging of ICG-p28 at nanomolar concentrations was able to detect the specific signals. We estimated the detection limit of the cell number in vitro. NIR-specific signals were detected from breast cancer cells as low as 200 cells in 1 mm size. Next, we evaluated ICG-p28 in multiple animal models. Athymic mice xenografted with MDA-MB-231 and IOWA-1T human breast cancer cells received a single injection of ICG-p28 i.v. at 0.5 mg/kg (=125 nmole/kg). Twenty-four hours after ICG-p28 injection, we observed the preferential uptake of ICG-p28 by tumors and a clear contrast between the tumor and the surrounding tissue. The histological analyses with H&E and Ki-67 staining on the set of tumor margin samples revealed that image-guided surgery with ICG-p28 could result in a clear negative margin at the edges of mammary tissues. Moreover, our imaging approach can also visually detect LN metastases (metastatic breast cancer in lymph nodes) through the preferential uptake of ICG-p28 concentrated over a period of time in small (∼1 mm) LN metastases. Overall, this nontoxic, and cost-effective method can offer a new approach that enables surgeons to identify tumor margins intraoperatively and potentially improves overall outcomes for breast cancer patients. Citation Format: Sunam Mander, Duy Binh Tran, Goto Masahide, Konstantin Christov, Albert Green, Tapas K. Das Gupta, Tohru Yamada. Image-guided surgery with a new optical probe for breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 2533.