利用靶向肿瘤细胞膜结合型 HSP70 的多肽示踪剂 TPP-IRDye800 提高人头颈癌的离体荧光成像效果。
Improved ex vivo fluorescence imaging of human head and neck cancer using the peptide tracer TPP-IRDye800 targeting membrane-bound Hsp70 on tumor cells.
机构信息
Department of Otolaryngology - Head and Neck Surgery, Technical University of Munich (TUM), School of Medicine and Health, TUM University Hospital, Munich, Germany.
Department of Radiation Oncology and Central Institute for Translational Cancer Research (TranslaTUM), Technical University of Munich (TUM), School of Medicine and Health, TUM University Hospital, Munich, Germany.
出版信息
Br J Cancer. 2024 Dec;131(11):1814-1824. doi: 10.1038/s41416-024-02872-8. Epub 2024 Oct 15.
BACKGROUND
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.
METHODS
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.
RESULTS
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.
CONCLUSION
TPP-IRDye800 is a promising fluorescence imaging probe for HNSCC.
背景
头颈部鳞状细胞癌（HNSCC）手术的主要目标是最大限度地保留正常组织的情况下，完全切除肿瘤细胞。膜 HSP70 靶向荧光标记肽 TPP-IRDye800 代表了一种很有前途的实时术中肿瘤可视化工具，能够检测到真正的肿瘤边界、高级别异型增生的临界岛和 LN 转移。
方法
采用 FITC 标记的 mAb cmHsp70.1 和 TPP 通过流式细胞术和荧光显微镜检测 HNSCC 细胞系和原发性 HNSCC 中的膜 HSP70（mHsp70）表达。将 TPP-IRDye800 喷涂在免疫组织化学证实的 HNSCC 和 LN 转移的新鲜切除肿瘤标本上进行肿瘤成像。使用 TPP-IRDye800 和识别 EGFR 的 Cetuximab-IRDye680 比较 TBR。
结果
体外表达 mHsp70 的 HNSCC 细胞特异性结合和内化 TPP。原发性 HNSCC 的 TPP-IRDye800 的 TBR（2.56±0.39）和 AUC[0.98 CI，0.95-1.00 与 0.91 CI，0.85-0.97]明显高于 Cetuximab-IRDye680（1.61±0.39）（p=0.0068），TPP-IRDye800 提供了更好的肿瘤描绘。荧光成像的 AUC 值高于外科医生的视觉检查[0.97 CI，0.94-1.00 与 0.92 CI，0.88-0.97]（p=0.048）。TPP-IRDye800 可用于可视化 LN 转移。使用临床应用的 KARL-STORZ 成像系统证实了实时组织描绘。
结论
TPP-IRDye800 是一种很有前途的 HNSCC 荧光成像探针。
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