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

TL;DR

This study characterizes a rat model of pancreatic cancer, showing it has features similar to human pancreatic cancer and is useful for imaging and therapy research.

Contribution

The study provides a detailed characterization of the DSL-6A/C1 rat model for pancreatic cancer, highlighting its suitability for 68Ga-FAPI imaging and therapeutic studies.

Findings

DSL-6A/C1 tumors display PDAC features like malformed ductal cells and cancer-associated fibroblasts.

The tumor microenvironment shows increased CD8+ T cells and decreased CD4+ T cells.

68Ga-FAPI PET imaging shows strong tracer uptake in tumor tissues.

Abstract

In this study, a rat model of pancreatic ductal adenocarcinoma (PDAC) was established and extensively analyzed. The histological examination confirmed that the model displayed features of PDAC, such as malformed malignant ductal cells and cancer-associated fibroblasts (CAFs). The study delved into the tumor microenvironment, revealing a unique immune profile with increased CD8+ cytotoxic T cells, suggesting a stronger anti-tumor immune response. Different imaging techniques were employed, showing contrast enhancement on MRI and a strong uptake of 68Ga-FAPI (fibroblast activation protein inhibitor) tracers in tumor tissues. This model’s suitability for further research in 68Ga-FAPI imaging and therapeutic approaches was highlighted. While some limitations exist, such as late-stage edema and heterogeneous growth patterns, this model provides valuable insights for PDAC studies and potential therapeutic strategies.

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 68Ga-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 68Ga-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 68Ga-FAPI-46 sensitivity, is a suitable alternative to established small animal models for many forms of preclinical analyses and therapeutic studies of PDAC.

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