A review on the use of radionuclide imaging techniques to detect margin positivity in intraoperative specimens during breast-conserving surgery.

Aaditya SinhaArnie Purushotham^*

• King's College London, London, United Kingdom

Introduction Achieving negative margins during breast-conserving surgery (BCS) for breast cancer is critical to reduce re-excision rates and minimise local recurrence. Intraoperative imaging techniques using radiotracers such as 18F-fluorodeoxyglucose (18F-FDG) offer a promising solution. When administered intravenously, 18F-FDG accumulates preferentially in malignant tissues due to their elevated glycolytic activity, enabling molecular imaging of tumour margins. Technologies such as Cerenkov Luminescence Imaging (CLI), Flexible Autoradiography (FAR), and intraoperative PET/CT systems have emerged as tools to visualise radiotracer distribution in excised breast tissue, offering real-time insight into margin status. Materials and Methodology CLI operates on the principle of detecting visible light photons generated by positrons from 18F-FDG travelling faster than light in tissue. FAR captures beta particles via a scintillating film to yield high-resolution surface maps of tracer activity. These modalities were evaluated both independently and in combination (CLI-FAR) using the LightPath® system, while the XEOS AURA 10 system was utilised for intraoperative PET/CT imaging. A series of feasibility studies and interventional trials assessed their diagnostic performance in real-time margin assessment during BCS. Results Grootendorst et al. (2017) demonstrated that CLI achieved 89% sensitivity and 95% specificity in identifying positive margins in a cohort of 12 patients. Jurrius et al. (2021) reported 81.7% sensitivity and 46.2% specificity with FAR in 66 patients. The CLI-FAR technique, by Sinha et al. (2024), yielded 76.9% sensitivity and 97.8% specificity, reducing re-excision rates by 69%. PET/CT-based intraoperative imaging using the AURA 10 device, as evaluated by De Crem et al. (2024), achieved 91% sensitivity and 94% specificity, while Göker et al. (2020) reported 79% sensitivity and 72% specificity using micro-PET/CT. Radiation exposure to surgical staff across studies remained low (15– 38 µSv), and imaging added minimal time to operative workflows. Conclusion Radionuclide-based intraoperative specimen imaging offers a viable, real-time solution for margin assessment in BCS. Techniques such as CLI, FAR, and intraoperative PET/CT demonstrate a strong correlation with histopathology, with the potential to significantly reduce re-excision rates. Challenges remain in imaging larger specimens and tumours with low metabolic activity. However, integrating these technologies into surgical practice presents a transformative opportunity for precision-guided oncologic surgery.