利用局部应用、酯酶激活成像剂在乳腺癌手术中体外荧光引导切缘评估

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

PHARMACOLOGICAL RESEARCH

影响因子:10.5

分区:医学2区 Top / 药学1区

发表日期:2024 Nov

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

DOI: 10.1016/j.phrs.2024.107464

摘要

在乳腺保乳手术（BCS）后，约有40 %的乳腺癌患者存在阳性切缘（TPRM，即切除标本表面存在癌细胞），需进行再次切除或加强放疗。为了避免这些额外治疗，可在手术中利用近红外（NIR）荧光成像技术，结合局部应用、酯酶激活的成像剂AKRO-6qcICG，检测TPRM并引导额外切除。本研究中，将该成像剂局部涂覆于新鲜切除的乳腺癌标本的所有表面（n=11例患者）及其厚度为3-5毫米的组织切片（n=26例患者），并获取其NIR荧光图像，与最终组织学结果进行相关分析。AKRO-6qcICG检测TPRM的灵敏度、特异性、阳性预测值（PVV）和阴性预测值（NPV）分别为100 %、67 %、10 %和100 %。在组织切片中，荧光信号的肿瘤对背景比例中位数为1.8。结果显示，局部应用的AKRO-6qcICG能高敏感性和NPV地在体外可视化TPRM，且具有足够的对比度，能区分邻近的正常乳腺组织。

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.