Heid I, Trajkovic-Arsic M, Gretzinger M,Kosanke Y,Steingoetter A, Rummeny EJ , Schmid RM, Siveke JT and Braren R. (01-05-2011).

Department: 

Research Area C

Abstract: 

Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease due to the late diagnosis and the lack of effective chemo/radiotherapy. The development of strategies for early tumor detection and evaluation of new treatments in models with high predictive value is of outmost importance. To characterize the spontaneous course of tumor progression, we monitored tumor growth kinetics and physiology in genetically engineered mouse models (GEMMs) of PDAC by multiparametric magnetic resonance imaging (MRI).

For generation of conditional endogenous PDAC models, Ptfla^+/Cre mice were crossed to Kras^+/LSL-G12D (K)Tgfα(T), K;p53(P)^+/fl, K;P^fl/fl, K;P^+/R172H;T and K;P^+/fl;T GEMMs and subjected to serial T2- weighted (T2w) MRI from 4-6 weeks of age onwards. Upon detection of solid tumor, diffusion- weighted imaging and dynamic contrast enhanced-MRI protocols were implemented. Survival analysis and histopathological characterization of PDAC were performed and correlated with MRI data. Tumor growth kinetics as determined by semi-automated segmentation of TIW data showed good correlation with the animal genotype. In K;P^+/fl animals, tumors were first detected at 12-15 weeks of age while significant tumor burden was observed around weck 20. Tumor appearance was highly heterogeneous, with cystic and solid tumor parts clearly distinguishable. Additional TGFα overexpression led to earlier onset, faster tumor growth and significantly shorter lifespan.