In vivo 18F-fluorodeoxyglucose-positron emission tomography/computed tomography imaging of pancreatic tumors in a transgenic rat model carrying the human KRASG12V oncogene

Abstract

Abstract.A novel KRAS-mediated transgenic rat model has previously been demonstrated, in which animals develop multiple pancreatic ductal adenocarcinoma (PDAC) that is histologically similar to human PDAC within two weeks. Positron emission tomography (PET)/computed tomography (CT) is commonly used for the diagnosis and staging of PDAC in humans, and can be adopted for optimal use in animal experiments. The aim of the present study was to evaluate the carcinogenic process in a rat pancreatic carcinoma model using small-animal multimodality imaging systems. The utility of fluorodeoxyglucose (FDG)-PET/CT in detecting the location and size of PDAC during tumor development in the present transgenic rat model was assessed. A small animal multimodality PET/CT system and contrast-enhanced CT (CECT) system were used for the imaging analysis of KRAS G12V male transgenic rats (n=6), which developed pancreatic tumors following the administration of an injection of Cre recombinase (Cre)-carrying adenovirus. Laparotomies performed at six weeks post-treatment revealed that all three (100%) Cre-expressing rats developed pancreatic tumors that were <2 mm in diameter, none of which were detected by 18 F-FDG PET/CT or CECT. At eight weeks post-treatment, the pancreatic tumors were heterogeneously visualized by 18 F-FDG-PET/CT and CECT in two of the three rats. Furthermore, the autopsies confirmed that all three rats had developed pancreatic tumors. These novel findings provide evidence that the FDG-PET/CT imaging system is a valuable tool for the evaluation of the carcinogenic process, and one which may aid in treatment and preventive methods for pancreatic tumors in mammalian models. A limitation associated with the early detection of PDACs warrants further investigation. IntroductionWith >250,000 annual mortalities, pancreatic carcinoma is one of the most lethal malignancies, ranking 12th worldwide (1). Mortality resulting from this disease is high even in developed countries, including Japan, the United Kingdom, France and the United States (2,3). Overall, >75% of pancreatic carcinoma cases are histologically characterized as pancreatic ductal adenocarcinoma (PDAC) (4,5). The majority of cases of PDAC are incurable due to the necessity of extensive resection, which is often not feasible, and due to the fact that the disease is rarely identified at an early stage. Furthermore, the majority of patients with advanced PDAC either do not respond, or respond transiently to chemotherapeutic drugs and radiation (6). Typically, the majority of patients with PDAC succumb to the disease within one year of diagnosis, and the overall five-year survival rate is <5% (7). Even in patients with resectable carcinoma, the long-term outcome remains unsatisfactory due to the incidence of early recurrence following surgical resection.In order to gain an improved understanding of this lethal malignant carcinoma, studies that use animal PDAC models with pancreatic neoplasms that resemble human PDAC are usually desirable. By focusing on human pancreat...