Abstract 5785: A novel technique for rapid intra-operative assessment of margins and sentinel lymph node metastasis status in human breast-conserving surgery

Purpose: The swift and precise evaluation of margin and sentinel lymph node (SLN) metastasis status during breast-conserving surgery is imperative in minimizing the likelihood of requiring additional surgical procedures. Near-infrared optical molecular imaging technology has been extensively utilized in the realm of surgical navigation, representing a significant advancement in the field of surgical oncology. However, due to safety and other concerns, very few effective probes can be applied to clinical trials, hindering the clinical implementation of fluorescence imaging. In this study, a novel technology was developed to rapidly identify tumor areas in vivo and ex vivo during surgical procedures, and delineate tumor boundaries and SLN metastases to assist surgeons in intraoperative decision-making. Methods: For animal studies, an orthotopic breast cancer mouse model, a spontaneous breast cancer transgenic mouse model, and a SLN metastasis mouse model of breast cancer were established. The tumor tissues and SLNs of mouse models above were surgically removed and incubated with a probe of different concentrations for different incubation time, then imaged by a second near-infrared window fluorescence imaging system. For clinical samples, surgically removed breast tissues and SLNs from 13 breast cancer patients were incubated with the targeting probe immediately after intraoperative resection and imaged to identify the tumor area and distinguish the tumor boundary and metastatic SLNs. The accuracy of fluorescence imaging was validated through pathological examination. Results: The ex vivo animal imaging experiments showed a fluorescence enhancement of tumor tissue and metastatic SLNs. For clinical samples, our results showed that this new technology yielded more than 90 % sensitivity and specificity in identifying the tumor area in the resected breast tissue. The average fluorescence tumor-to-normal ratios were more than three in different incubation conditions. Furthermore, we also used this technique to image metastatic SLNs intra-operatively and showed that metastatic SLNs exhibited a nearly 3-fold increase in fluorescence signal compared to benign SLNs. Calculations on the results of the fluorescence signal in relation to the metastatic status of SLNs yielded values of more than 90 % for sensitivity and specificity. Conclusions: The utilization of fluorescently labeled ADC that specifically targets tumor surface proteins combined with intraoperative fluorescence imaging has effectively delineated boundaries in breast cancer specimens and facilitated the detection of metastatic SLNs. This approach has the potential to inform decisions regarding optimal resection strategies in oncology, particularly within the constraints of a limited surgical window. Citation Format: Wei-ling Chen, Yuan-yuan Zhu, Zhao Wu, Jun-hong Chen, Ting-wen Guo, Li-xin Zhang, Guo-jun Zhang. A novel technique for rapid intra-operative assessment of margins and sentinel lymph node metastasis status in human breast-conserving surgery [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 5785.