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, and68Ga-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 with68Ga-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, and68Ga-FAPI-46 sensitivity, is a suitable alternative to established small animal models for many forms of preclinical analyses and therapeutic studies of PDAC.
在Lewis大鼠中建立了DSL-6A/C1小鼠胰腺导管腺癌（PDAC）肿瘤模型，并通过多参数综合分析进行表征，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，研究肿瘤微环境中免疫细胞的分布情况。采用多参数磁共振成像（MRI）和正电子发射断层扫描（PET）对肿瘤进行表征，并使用靶向癌症相关成纤维细胞（CAFs）的68Ga-FAPI-46验证组织学发现。组织学分析证实了典型的PDAC特征，如畸形的胰腺导管恶性细胞和CAFs。研究发现独特的免疫景观，显示肿瘤微环境中CD8+T细胞增多而CD4+T细胞减少。使用68Ga-FAPI示踪剂的PET成像显示肿瘤组织中有强烈的示踪剂摄取。MRI参数表明，随着时间的推移，病灶内坏死增加，且存活肿瘤区域的对比剂摄取升高。我们证明，DSL-6A/C1肿瘤模型，特别是由于其高致瘤性、肿瘤大小和对68Ga-FAPI-46的敏感性，是许多形式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。
Multiparametric Characterization of the DSL-6A/C1 Pancreatic Cancer Model in Rats
肿瘤(癌症)患者之家