Ex vivo fluorescence-guided resection margin assessment in breast cancer surgery using a topically applied, cathepsin-activatable imaging agent

• Published in: Pharmacological research Vol. 209; p. 107464
• Main Authors: Linders, Daan G.J., Bijlstra, Okker D., Walker, Ethan, March, Taryn L., Pool, Martin, Valentijn, A. Rob P.M., Dijkhuis, Tom H., Woltering, Jikke N., Pijl, Floor R., Noordam, Gilbert, van den Burg, Davey, van der Sijp, Joost R.M., Guicherit, Onno R., Marinelli, Andreas W.K.S., Burggraaf, Jacobus, Rissmann, Robert, Bogyo, Matthew, Hilling, Denise E., Kuppen, Peter J.K., Straight, Brian, Straver, Marieke E., Hazelbag, Hans Marten, Basilion, James P., Vahrmeijer, Alexander L.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01.11.2024
• Subjects: Activatable probes; Breast cancer; Cathepsins; Fluorescence-guided surgery; Topical application; Cathepsins; Breast cancer; Activatable probes; Topical application; Fluorescence-guided surgery
• ISSN: 1043-6618; 1096-1186; 1096-1186
• DOI: 10.1016/j.phrs.2024.107464

Up to 40 % of breast cancer patients have a tumor-positive resection margin (TPRM) – defined as cancer cells at the surface of the resected specimen – after breast-conserving surgery (BCS), necessitating re-resection or boost radiation. To prevent these additional treatments, intraoperative near-infrared (NIR) fluorescence imaging with the topically applied, cathepsin-activatable imaging agent AKRO-6qcICG might be used to detect TPRMs and guide additional resection. Here, to validate its performance, the agent is topically applied to all surfaces of freshly resected breast cancer specimens (n = 11 patients) and to 3–5 mm thick tissue slices of the specimens (n = 26 patients). NIR fluorescence images of the resection surfaces and tissue slices are acquired and correlated to final histopathology. AKRO-6qcICG detects TPRMs with a sensitivity, specificity, PVV, and NPV of 100 %, 67 %, 10 %, and 100 %, respectively. On the tissue slices, the fluorescence signal has a median tumor-to-background ratio of 1.8. These findings indicate that topically applied AKRO-6qcICG can visualize TPRMs ex vivo with a high sensitivity and NPV, with sufficient contrast to adjacent healthy breast tissue. [Display omitted]