使用针对肿瘤细胞上膜结合 Hsp70 的肽示踪剂 TPP-IRDye800，改进了人类头颈癌的离体荧光成像。
Improved ex vivo fluorescence imaging of human head and neck cancer using the peptide tracer TPP-IRDye800 targeting membrane-bound Hsp70 on tumor cells.
发表日期：2024 Oct 15
作者：
Katharina L K Holzmann, Johanna L Wolf, Stefan Stangl, Philipp Lennartz, Atsuko Kasajima, Carolin Mogler, Bernhard Haller, Eva-Vanessa Ebert, Daniel Jira, Maren L A Lauterbach, Franziska von Meyer, Leonhard Stark, Leonie Mauch, Benedikt Schmidl, Barbara Wollenberg, Gabriele Multhoff, Markus Wirth
来源：
BRITISH JOURNAL OF CANCER
摘要：
HNSCC 手术的主要目标是完全切除肿瘤细胞，最大限度地保留正常组织。膜 Hsp70 靶向荧光标记肽 TPP-IRDye800 是一种很有前途的实时术中肿瘤可视化工具，能够检测真实的肿瘤边缘、高度不典型增生的关键岛和 LN 转移。 HNSCC 上的膜 Hsp70 (mHsp70) 表达使用 FITC 结合的 mAb cmHsp70.1 和 TPP，通过流式细胞术和荧光显微镜测定细胞系和原发性 HNSCC。将 TPP-IRDye800 喷洒在经免疫组织化学证实的 HNSCC 和 LN 转移瘤的新鲜切除肿瘤材料上进行肿瘤成像。使用 TPP-IRDye800 和 Cetuximab-IRDye680 比较 TBR，识别表达 EGFR.mHsp70 的 HNSCC 细胞在体外特异性结合和内化 TPP。 TPP-IRDye800 对原发性 HNSCC 的 TBR (2.56±0.39) 和 AUC [0.98 CI, 0.95-1.00 vs. 0.91 CI, 0.85-0.97] 显着高于西妥昔单抗-IRDye680 (1.61±0.39) (p = 0.0068) ）和TPP-IRDye800 提供了更好的肿瘤轮廓。荧光成像显示的 AUC 值高于外科医生的目视检查 [0.97 CI, 0.94-1.00 vs. 0.92 CI, 0.88-0.97] (p = 0.048)。使用 TPP-IRDye800 可以可视化 LN 转移。使用临床应用的 KARL-STORZ 成像系统确认了实时组织描绘。TPP-IRDye800 是一种很有前途的 HNSCC 荧光成像探针。© 2024。作者。
The primary goal of surgery in HNSCC is the complete resection of tumor cells with maximum preservation of normal tissue. The membrane Hsp70-targeting fluorescence labelled peptide TPP-IRDye800 represents a promising tool for real-time intraoperative tumor visualization, enabling the detection of true tumor margins, critical isles of high-grade dysplasia and LN metastases.Membrane Hsp70 (mHsp70) expression on HNSCC cell lines and primary HNSCC was determined by flow cytometry and fluorescence microscopy using FITC-conjugated mAb cmHsp70.1 and TPP. TPP-IRDye800 was sprayed on freshly resected tumor material of immunohistochemically confirmed HNSCC and LN metastases for tumor imaging. TBRs were compared using TPP-IRDye800 and Cetuximab-IRDye680, recognizing EGFR.mHsp70 expressing HNSCC cells specifically bind and internalize TPP in vitro. The TBR (2.56 ± 0.39) and AUC [0.98 CI, 0.95-1.00 vs. 0.91 CI, 0.85-0.97] of TPP-IRDye800 on primary HNSCC was significantly higher than Cetuximab-IRDye680 (1.61 ± 0.39) (p = 0.0068) and TPP-IRDye800 provided a superior tumor delineation. Fluorescence imaging showed higher AUC values than a visual inspection by surgeons [0.97 CI, 0.94-1.00 vs. 0.92 CI, 0.88-0.97] (p = 0.048). LN metastases could be visualized using TPP-IRDye800. Real-time tissue delineation was confirmed using the clinically applied KARL-STORZ imaging system.TPP-IRDye800 is a promising fluorescence imaging probe for HNSCC.© 2024. The Author(s).