A major limitation in the pharmacological treatment of clinically detectable primary cancers and their metastases is their limited accessibility to anti-cancer drugs (cytostatics, inhibitory antibodies, small-molecule inhibitors) critically impairing therapeutic efficacies. Investigations on the tissue distribution of such drugs are rare and have only been based on fresh frozen material or methanol-fixed cell culture cells so far. In this paper, we expand the detection of cisplatin-induced DNA adducts and anthracyclines as well as therapeutic antibodies to routinely prepared formalin-fixed, paraffin-embedded sections (FFPE). Using pre-treated cell lines prepared as FFPE samples comparable to tissues from routine analysis, we demonstrate that our method allows for the detection of chemotherapeutics (anthracyclines by autofluorescence, cisplatin by immune detection of DNA adducts) as well as therapeutic antibodies. This methodology thus allows for analyzing archival FFPE tissues, as demonstrated here for the detection of cisplatin, doxorubicin and trastuzumab in FFPE sections of tumor xenografts from drug-treated mice. Analyzing human tumor samples, this will lead to new insights into the tissue penetration of drugs.

中文翻译：

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在福尔马林固定石蜡包埋的人类癌细胞中检测阿霉素，顺铂和治疗性抗体。

在临床上可检测到的原发癌及其转移的药物治疗中，主要的局限性是它们与抗癌药物（细胞生长抑制剂，抑制性抗体，小分子抑制剂）的可及性有限，严重损害了治疗效果。迄今为止，对这种药物的组织分布的研究很少，并且仅基于新鲜的冷冻材料或甲醇固定的细胞培养细胞。在本文中，我们扩展了对常规制备的福尔马林固定石蜡包埋切片（FFPE）的顺铂诱导的DNA加合物和蒽环类化合物以及治疗性抗体的检测。使用预处理后的细胞系作为FFPE样品，可与常规分析中的组织进行比较，我们证明了我们的方法可检测化学疗法（蒽环类药物通过自发荧光，免疫检测DNA加合物产生的顺铂）以及治疗性抗体。因此，该方法可以分析档案FFPE组织，如此处所示，用于检测药物治疗小鼠的异种移植物FFPE切片中的顺铂，阿霉素和曲妥珠单抗。分析人类肿瘤样本，这将导致对药物组织渗透的新见解。