TY - JOUR
T1 - Ex vivo fluorescence-guided resection margin assessment in breast cancer surgery using a topically applied, cathepsin-activatable imaging agent
AU - Linders, Daan G.J.
AU - Bijlstra, Okker D.
AU - Walker, Ethan
AU - March, Taryn L.
AU - Pool, Martin
AU - Valentijn, A. Rob P.M.
AU - Dijkhuis, Tom H.
AU - Woltering, Jikke N.
AU - Pijl, Floor R.
AU - Noordam, Gilbert
AU - van den Burg, Davey
AU - van der Sijp, Joost R.M.
AU - Guicherit, Onno R.
AU - Marinelli, Andreas W.K.S.
AU - Burggraaf, Jacobus
AU - Rissmann, Robert
AU - Bogyo, Matthew
AU - Hilling, Denise E.
AU - Kuppen, Peter J.K.
AU - Straight, Brian
AU - Straver, Marieke E.
AU - Hazelbag, Hans Marten
AU - Basilion, James P.
AU - Vahrmeijer, Alexander L.
N1 - Publisher Copyright: © 2024 The Authors
PY - 2024/11
Y1 - 2024/11
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85206177707&partnerID=8YFLogxK
U2 - 10.1016/j.phrs.2024.107464
DO - 10.1016/j.phrs.2024.107464
M3 - Article
C2 - 39401538
AN - SCOPUS:85206177707
SN - 1043-6618
VL - 209
JO - Pharmacological Research
JF - Pharmacological Research
M1 - 107464
ER -
