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. 2024 Nov:209:107464.
doi: 10.1016/j.phrs.2024.107464. Epub 2024 Oct 12.

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

Daan G J Linders  1 , Okker D Bijlstra  1 , Ethan Walker  2 , Taryn L March  1 , Martin Pool  3 , A Rob P M Valentijn  3 , Tom H Dijkhuis  1 , Jikke N Woltering  1 , Floor R Pijl  1 , Gilbert Noordam  4 , Davey van den Burg  4 , Joost R M van der Sijp  5 , Onno R Guicherit  5 , Andreas W K S Marinelli  5 , Jacobus Burggraaf  6 , Robert Rissmann  6 , Matthew Bogyo  7 , Denise E Hilling  8 , Peter J K Kuppen  1 , Brian Straight  9 , Marieke E Straver  5 , Hans Marten Hazelbag  4 , James P Basilion  10 , Alexander L Vahrmeijer  11
Affiliations

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

Daan G J Linders et al. Pharmacol Res. 2024 Nov.

Abstract

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.

Keywords: Activatable probes; Breast cancer; Cathepsins; Fluorescence-guided surgery; Topical application.

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Conflict of interest statement

Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: James P. Basilion reports financial support was provided by National Institutes of Health. Matthew Bogyo reports financial support was provided by National Institutes of Health. James P. Basilion reports a relationship with Akrotome Imaging that includes: board membership, consulting or advisory, equity or stocks, funding grants, and travel reimbursement. Matthew Bogyo reports a relationship with Akrotome Imaging that includes: board membership, consulting or advisory, equity or stocks, funding grants, and travel reimbursement. Brian Straight reports a relationship with Akrotome Imaging that includes: employment, equity or stocks, funding grants, and travel reimbursement. James P. Basilion has patent licensed to Akrotome Imaging. Matthew Bogyo has patent licensed to Akrotome Imaging. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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