Ex vivo fluorescence-guided resection margin assessment in breast cancer surgery using a topically applied, cathepsin-activatable imaging agent
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.
Authors
- Matthew S. Bogyo (ORCID: https://orcid.org/0000-0003-3753-4412)
- Danny Burg
- Marieke E. Straver (ORCID: https://orcid.org/0000-0003-3052-318X)
- Daan G. J. Linders (ORCID: https://orcid.org/0000-0003-4524-4175)
- Taryn L. March
- Martin Pool (ORCID: https://orcid.org/0000-0002-4892-3109)
- Alexander L. Vahrmeijer (ORCID: https://orcid.org/0000-0001-9370-0011)
- A. Rob P.M. Valentijn
- Denise E. Hilling (ORCID: https://orcid.org/0000-0002-5875-6164)
- Ethan Walker (ORCID: https://orcid.org/0000-0002-5132-8191)
- Okker D. Bijlstra (ORCID: https://orcid.org/0000-0001-9069-500X)
- Peter J.K. Kuppen (ORCID: https://orcid.org/0000-0002-0294-3251)
- Tom H. Dijkhuis (ORCID: https://orcid.org/0009-0002-4794-5223)
- James P. Basilion
- Andreas Marinelli
- Brian Straight
- Hans Marten Hazelbag (ORCID: https://orcid.org/0009-0003-2182-6952)
- Jacobus Burggraaf (ORCID: https://orcid.org/0000-0001-7912-0918)
- Onno R. Guicherit (ORCID: https://orcid.org/0000-0003-4862-1394)
- Joost R.M. van der Sijp
- Robert Rißmann
- Gilbert Noordam
- Jikke N Woltering
- Floor R Pijl
Institutions
- Leiden University Medical Center (NL)
- Akrotome Imaging (United States) (US)
- Medisch Centrum Haaglanden (NL)
- Centre for Human Drug Research (NL)
- Erasmus MC Cancer Institute (NL)
- Case Western Reserve University (US)
- Stanford University (US)
Publication Details
- Journal
- Pharmacological Research
- Published
- 2024-10-12
- DOI
- https://doi.org/10.1016/j.phrs.2024.107464
- Citations
- 1
- Primary Topic
- Breast Cancer Treatment Studies
- Type
- article
- Field-Weighted Citation Impact
- 0.29
Funders
- Foundation for the National Institutes of Health
- Haaglanden Medisch Centrum
- National Institutes of Health