使用肽示踪剂tpp-ryye800靶向肿瘤细胞上的膜结合的HSP70，改善了人头和颈部癌的体内荧光成像
Improved ex vivo fluorescence imaging of human head and neck cancer using the peptide tracer TPP-IRDye800 targeting membrane-bound Hsp70 on tumor cells
影响因子:6.80000
分区:医学2区 Top / 肿瘤学2区
发表日期:2024 Dec
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
摘要
HNSCC手术的主要目的是完全切除肿瘤细胞，最大程度地保留正常组织。 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和荧光显微镜使用FITC偶联的MAB CMHSP70.1和TPP。将TPP-dryye800喷洒在新鲜切除的免疫组织化学确认的HNSCC和LN转移的肿瘤材料上，以进行肿瘤成像。使用TPP-riDYE800和cetuximab-dirye680比较TBR，识别表达HNSCC细胞的EGFR.MHSP70在体外特异性结合并内化了TPP。 tbr（2.56±0.39）和AUC [0.98 ci，0.95-1.00 vs. 0.91 CI，0.85-0.97] tpp-riDye800在原发性HNSCC上明显高于cetuximab-irdye680（1.61±0.39）（1.61±0.39）（p = 0.0068）和TUMOR ATH，TUMER yee8 Y00 yee8ye8yeye80 iryeyeyeyemeyememab-irdye680（1.61±0.39）和tumory。荧光成像显示的AUC值比外科医生的视觉检查更高[0.97 CI，0.94-1.00 vs. 0.92 CI，0.88-0.97]（p = 0.048）。 LN转移可以使用TPP-ryye800可视化。使用临床应用的Karl-Storz成像系统证实了实时组织描绘。TPP-ryye800是HNSCC的有希望的荧光成像探针。
Abstract
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.