使用局部应用的组织蛋白酶激活显像剂在乳腺癌手术中进行体外荧光引导切除边缘评估。
Ex vivo fluorescence-guided resection margin assessment in breast cancer surgery using a topically applied, cathepsin-activatable imaging agent.
发表日期：2024 Oct 12
作者：
Daan G J Linders, Okker D Bijlstra, Ethan Walker, Taryn L March, Martin Pool, A Rob P M Valentijn, Tom H Dijkhuis, Jikke N Woltering, Floor R Pijl, Gilbert Noordam, Davey van den Burg, Joost R M van der Sijp, Onno R Guicherit, Andreas W K S Marinelli, Jacobus Burggraaf, Robert Rissmann, Matthew Bogyo, Denise E Hilling, Peter J K Kuppen, Brian Straight, Marieke E Straver, Hans Marten Hazelbag, James P Basilion, Alexander L Vahrmeijer
来源：
PHARMACOLOGICAL RESEARCH
摘要：
高达 40% 的乳腺癌患者在保乳手术 (BCS) 后出现肿瘤阳性切除边缘 (TPRM)（定义为切除样本表面的癌细胞），需要再次切除或加强放疗。为了防止这些额外的治疗，可使用局部应用的组织蛋白酶激活成像剂 AKRO-6qcICG 进行术中近红外 (NIR) 荧光成像来检测 TPRM 并指导额外的切除。在这里，为了验证其性能，将该试剂局部应用于新切除的乳腺癌标本（n = 11 名患者）的所有表面以及 3-5 毫米厚的标本组织切片（n = 26 名患者）。获取切除表面和组织切片的近红外荧光图像并与最终的组织病理学相关。 AKRO-6qcICG 检测 TPRM 的灵敏度、特异性、PVV 和 NPV 分别为 100%、67%、10% 和 100%。在组织切片上，荧光信号的肿瘤与背景比率中值为 1.8。这些研究结果表明，局部应用 AKRO-6qcICG 可以以高灵敏度和 NPV 离体可视化 TPRM，并与邻近的健康乳腺组织形成足够的对比度。版权所有 © 2024 作者。由爱思唯尔有限公司出版。保留所有权利。
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.Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.