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Multiparametric Characterization of the DSL-6A/C1 Pancreatic Cancer Model in Rats.

Patrick SchmidtJohannes LindemeyerPranali RautMarkus SchützSven SaniternikJannika JönssonHeike EndepolsThomas FischerAlexander QuaasHans Anton SchlößerMartin ThelenJuan Daniel Castillo-Gómez
Published in: Cancers (2024)
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 68 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 68 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 68 Ga-FAPI-46 sensitivity, is a suitable alternative to established small animal models for many forms of preclinical analyses and therapeutic studies of PDAC.
Keyphrases
  • magnetic resonance imaging
  • contrast enhanced
  • pet imaging
  • computed tomography
  • pet ct
  • magnetic resonance
  • gene expression
  • oxidative stress
  • signaling pathway
  • bone marrow
  • cell proliferation
  • cell death