Image-guided surgery with a new tumour-targeting probe improves the identification of positive margins.

Masahide Goto, Ingeun Ryoo, Samer Naffouje, Sunam Mander, Konstantin Christov, Jing Wang, Albert Green, Anne Shilkaitis, Tapas K Das Gupta, Tohru Yamada

EBioMedicine 2022 Feb

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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 the increasing cases of BCS, a novel method of complete tumour removal at the initial surgical resection is critically needed in the operating room to help optimize the surgical procedure and to confirm tumour-free edges. We developed a unique near-infrared (NIR) fluorescence imaging probe, ICG-p28, composed of the clinically nontoxic tumour-targeting peptide p28 and the FDA-approved NIR dye indocyanine green (ICG). ICG-p28 was characterized in vitro and evaluated in multiple breast cancer animal models with appropriate control probes. Our experimental approach with multiple-validations and -blinded procedures was designed to determine whether ICG-p28 can accurately identify tumour margins in mimicked intraoperative settings. The in vivo kinetics were analysed to optimize settings for potential clinical use. Xenograft tumours stably expressing iRFP as a tumour marker showed significant colocalization with ICG-p28, but not ICG alone. Image-guided surgery with ICG-p28 showed an over 6.6 × 103-fold reduction in residual normalized tumour DNA at the margin site relative to control approaches (i.e., surgery with ICG or palpation/visible inspection alone), resulting in an improved tumour recurrence rate (92% specificity) in multiple breast cancer animal models independent of the receptor expression status. ICG-p28 allowed accurate identification of tumour cells in the margin to increase the complete resection rate. Our simple and cost-effective approach has translational potential and offers a new surgical procedure that enables surgeons to intraoperatively identify tumour margins in a real-time, 3D fashion and that notably improves overall outcomes by reducing re-excision rates. This work was supported by NIH/ National Institute of Biomedical Imaging and Bioengineering, R01EB023924. Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.

Citation

Masahide Goto, Ingeun Ryoo, Samer Naffouje, Sunam Mander, Konstantin Christov, Jing Wang, Albert Green, Anne Shilkaitis, Tapas K Das Gupta, Tohru Yamada. Image-guided surgery with a new tumour-targeting probe improves the identification of positive margins. EBioMedicine. 2022 Feb;76:103850