Schmidt Patrick, Lindemeyer Johannes, Raut Pranali, Schütz Markus, Saniternik Sven, Jönsson Jannika, Endepols Heike, Fischer Thomas, Quaas Alexander, Schlößer Hans Anton, Thelen Martin, Grüll Holger
Faculty of Medicine and University Hospital of Cologne, Institute of Diagnostic and Interventional Radiology, University of Cologne, 50937 Cologne, Germany.
Faculty of Mathematics and Natural Sciences, Department of Chemistry, University of Cologne, 50937 Cologne, Germany.
Cancers (Basel). 2024 Apr 17;16(8):1535. doi: 10.3390/cancers16081535.
The DSL-6A/C1 murine pancreatic ductal adenocarcinoma (PDAC) tumor model was established in Lewis rats and characterized through a comprehensive multiparametric analysis to compare it to other preclinical tumor models and explore potential diagnostic and therapeutical targets. DSL-6A/C1 tumors were histologically analyzed to elucidate PDAC features. The tumor microenvironment was studied for immune cell prevalence. Multiparametric MRI and PET imaging were utilized to characterize tumors, and Ga-FAPI-46-targeting cancer-associated fibroblasts (CAFs), were used to validate the histological findings. The histology confirmed typical PDAC characteristics, such as malformed pancreatic ductal malignant cells and CAFs. Distinct immune landscapes were identified, revealing an increased presence of CD8 T cells and a decreased CD4 T cell fraction within the tumor microenvironment. PET imaging with Ga-FAPI tracers exhibited strong tracer uptake in tumor tissues. The MRI parameters indicated increasing intralesional necrosis over time and elevated contrast media uptake in vital tumor areas. We have demonstrated that the DSL-6A/C1 tumor model, particularly due to its high tumorigenicity, tumor size, and Ga-FAPI-46 sensitivity, is a suitable alternative to established small animal models for many forms of preclinical analyses and therapeutic studies of PDAC.
DSL-6A/C1小鼠胰腺导管腺癌(PDAC)肿瘤模型在Lewis大鼠中建立,并通过全面的多参数分析进行表征,以与其他临床前肿瘤模型进行比较,并探索潜在的诊断和治疗靶点。对DSL-6A/C1肿瘤进行组织学分析以阐明PDAC特征。研究肿瘤微环境中的免疫细胞流行情况。利用多参数MRI和PET成像对肿瘤进行表征,并使用靶向Ga-FAPI-46的癌症相关成纤维细胞(CAF)来验证组织学结果。组织学证实了典型的PDAC特征,如畸形的胰腺导管恶性细胞和CAF。确定了不同的免疫格局,显示肿瘤微环境中CD8 T细胞的存在增加,CD4 T细胞比例降低。使用Ga-FAPI示踪剂的PET成像在肿瘤组织中显示出强烈的示踪剂摄取。MRI参数表明,随着时间的推移,瘤内坏死增加,重要肿瘤区域的造影剂摄取升高。我们已经证明,DSL-6A/C1肿瘤模型,特别是由于其高致瘤性、肿瘤大小和对Ga-FAPI-46的敏感性,是许多形式的PDAC临床前分析和治疗研究中已建立的小动物模型的合适替代品。