Abstract
PurposeTo investigate the feasibility of using multi-modality imaging to monitor the creation of rat models with orthotopic pancreatic head cancer with obstructive jaundice.Results27 of 52 rats (51.92%) developed pancreatic head cancer. The tumor formation rate was significantly higher in the animal group receiving bioluminescent tumor, compared to the group receiving non-bioluminescent donor tumors [78.1% (25/32 rats) vs 10.0% (2/20 rats), P = 0.0001]. Both ultrasound imaging and MRI clearly characterized the orthotopic tumors. Laboratory biochemistry test for those rats with obstructive jaundice showed elevated levels of bilirubin, aspartate transaminase (AST), alkaline phosphatase (ALT) and gamma-glutamyl transpeptidase (λ-GGT), compared with those rats without jaundice (P < 0.05). Correlative pathology confirmed that all tumors were ductal adenocarcinomas, and located in pancreatic head regions.Materials and MethodsRat pancreatic adenocarcinoma cells (DSL-6A/C1) were first transfected with lentivirus/mCherry-luciferase genes, and then subcutaneously implanted into flanks of donor immunocompetent Lewis rats, to create pancreatic tumor tissues. The tumor tissues from donor rats with either bioluminescence signal or without the signal were then transplanted into the pancreatic heads of 52 recipient Lewis rats. Bioluminescence optical and ultrasound imaging, as well as magnetic resonance imaging (MRI), were performed to follow up the tumor formation and growth in these tumor-transplanted rats. Physical examination and biochemistry test were used to discern the rats with obstructive jaundice. The rats were euthanized for subsequent histologic correlation and confirmation.ConclusionsWe successfully created a new rat model with orthotopic pancreatic head cancer, which can be accurately monitored and visualized by different imaging modalities.
Highlights
Pancreatic cancer is one of the most lethal and aggressive human malignancies
The tumor formation rate was significantly higher in the animal group receiving bioluminescent tumor, compared to the group receiving non-bioluminescent donor tumors [78.1% (25/32 rats) vs 10.0% (2/20 rats), P = 0.0001]
The implanted human pancreatic cancer xenografts can grow to a substantial tumor mass in the immunocompromised or severe combined immunodeficiency (SCID) mice within a relatively short period, which presents some values in preclinical studies to explore the alternative diagnosis and treatment methods for pancreatic cancers
Summary
Pancreatic cancer is one of the most lethal and aggressive human malignancies. It is the fourth most frequent cause of cancer-related deaths in the world, with an approximately 37,000 deaths in the United States in 2012 and 50,000 deaths per year in Western Europe [1, 2]. The implanted human pancreatic cancer xenografts can grow to a substantial tumor mass in the immunocompromised or severe combined immunodeficiency (SCID) mice within a relatively short period, which presents some values in preclinical studies to explore the alternative diagnosis and treatment methods for pancreatic cancers. Such models cannot reflect the interaction between the tumor and a fully competent immunologic system of the tumor host. These mouse models of pancreatic cancers are not suitable for the studies of developing the imaging-guided ablative therapies, such as interstitial radiofrequency ablation [1, 10, 11], microwave ablation [12, 13], laser ablation [14] and irreversible electroporation ablation [15], due to the tiny size of the pancreas of a mouse that does not fit in the requirement for placement of the clinically-used ablation electrodes
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