Improvement of DCIS resection using intraoperative imaging with ICG-p28

Patients with ductal carcinoma in situ (DCIS), the earliest form of breast cancer, are treated with breast-conserving surgery (BCS) when feasible. The primary objective of BCS is to completely resect a lesion with a tumor-free margin in a single surgery, as positive margins are a risk factor for local recurrence. However, re-excision rates due to positive margins are high. Since reported positive margin rates after BCS for DCIS and invasive breast cancer are 20-81% and 15-47%, respectively, new intraoperative intervention for BCS represents a medical unmet need to achieve adequate resection margins. We previously established a new near-infrared (NIR) fluorescence imaging probe ICG-p28 by utilizing indocyanine green (ICG) labeled with cell-penetrating peptide carrying a tumor-targeting motif, and demonstrated that our imaging approach accurately identified the tumor margins in invasive breast cancer animal models. We hypothesized that our imaging approach can be applied to DCIS and yield similar rates when compared with invasive breast cancer. Here, we report that the real-time imaging of DCIS mouse models using ICG-p28 showed significant improvement in tumor recurrence rates by clear tumor margin identification compared to a control agent, ICG alone. With the chemical and biological characteristics of ICG-p28, our promising approach holds translational potential for image-guided DCIS surgery, reducing re-excision and tumor recurrence rates through tumor margin identification.