Non-invasive dynamic monitoring initiation and growth of pancreatic tumor in the LSL-Kras(G12D/+);LSL-Trp53(R172H/+);Pdx-1-Cre (KPC) transgenic mouse model

摘要

The LSL-Kras(G12D/+);LSL-Trp53(R172H/+);Pdx-1-Cre (KPC) mouse is one of the most widely used transgenic models to evaluate tumor characteristics and to develop novel therapies for pancreatic ductal adenocarcinoma (PDAC). There is no report of the effective systemic evaluation of longitudinal KPC tumor imitation and growth. Therefore, we aimed to characterize the initiation and progression of pancreatic cancer in KPC mice using longitudinal multiparametric magnetic resonance imaging (MRI) approaches and overall survival. Ten KPC mice were used to develop spontaneous PDAC and monitored by MRI. Tumor growth was evaluated using weekly acquired MRI data. The relationship between diffusion-weighted MRI (DW-MRI) imaging biomarkers (apparent diffusion coefficient - ADC) and tumor fibrosis measurement by pathological methods was assessed by Pearson correlation coefficient. Six KPC mice developed spontaneously pancreatic tumors at the age of 20.0 +/- 2.9 weeks with a relatively short life span (6.8 +/- 1.8 weeks). The tumors could be detected by MRI with a minimum diameter of 3.88 +/- 1.18 mm (range, 2.18-5.20 mm), showing a rapid growth curve according to both the longest diameter (1.63 +/- 0.52 mm/week) and tumor volume (148.77 +/- 80.87 mm(3))/week. Pathological results confirmed that the tumors display histopathological features of human pancreatic cancer. A strong correlation between ADC values and fibrosis measurements was observed (R = - 0.825, P = .043). Our results show that the initiation and progression of pancreatic tumor in KPC mice can be evaluated by longitudinally non-invasive dynamic MRI approaches. The findings will be the fundamental KPC background data for developing novel therapeutic approaches, in particular for evaluation of response to novel treatments.