乳腺癌手术中使用局部应用的，可抗蛋白酶激活的成像剂在乳腺癌手术中的离体荧光引导的切除率评估
Ex vivo fluorescence-guided resection margin assessment in breast cancer surgery using a topically applied, cathepsin-activatable imaging agent
影响因子:10.50000
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
摘要
多达40％的乳腺癌患者的肿瘤阳性切除缘（TPRM）定义为乳腺癌手术后切除标本表面的癌细胞（BCS），需要进行重新切除或增强辐射。为了防止这些其他处理，可以使用局部施加的，可施加的，可激活的成像剂Akro-6QCICG进行术中近红外（NIR）荧光成像来检测TPRMS并引导其他切除。在这里，为了验证其性能，该药物局部应用于新鲜切除的乳腺癌标本（n = 11例）和样品的3-5mm厚的组织切片（n = 26例）。获得切除表面和组织切片的NIR荧光图像并与最终组织病理学相关。 Akro-6QCICG分别以100％，67％，10％和100％的敏感性，特异性，PVV和NPV检测TPRM。在组织切片上，荧光信号的中位肿瘤与背景比为1.8。这些发现表明，局部应用Akro-6QCICG可以以高灵敏度和NPV的形式可视化TPRMS，与相邻健康的乳腺组织形成了足够的对比。
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.