Magnetic resonance imaging in an orthotopic rat model: Blockade of epidermal growth factor receptor with EMD72000 inhibits human pancreatic carcinoma growth

Abstract

The purpose of our research was to investigate the antiangiogenic effect of the epidermal growth factor receptor monoclonal antibody (anti-EGF-R MAB) EMD72000, in an orthotopic human pancreatic carcinoma model in rats, assessed by magnetic resonance (MR) imaging using angiogenic surrogate markers in comparison with histopathologic findings. Human pancreatic adenocarcinoma cells L3.6pl were injected orthotopically in the pancreas of 12 athymic nude rats. Through a 21-day course, groups of 6 rats were treated intraperitoneally with either EMD72000 or with saline solution for control animals. Dynamic contrast-enhanced MR imaging was performed before and after the treatment to assess microvascular permeability, estimated by the endothelial transfer coefficient (KPS) and fractional plasma volumes (fPV) of the pancreatic tumors. EMD72000-treated animals showed significantly less tumor volume progression (1,080 mm3 +/- 1,244; p = 0.012) and significantly lower values for microvascular permeability (KPS = 4.2 ml min(-1) 100 ml(-1) of tissue +/- 2.8; p = 0.015), fractional plasma volume (fPV = 0.018 ml ml(-1) of tissue +/- .015; p = 0.003) and microvessel density (MVD = 13 +/- 4 (0.159 mm2); p = 0.001) than saline-treated animals (6,544 mm3 +/- 5,202; 9.5 ml min(-1) 100 ml(-1) of tissue +/- 4.3, 0.056 ml ml(-1) of tissue +/- 0.019 and 25 +/- 5 (0.159 mm2), respectively). KPS and fPV values showed moderate positive correlation with MVD (r = 0.5, p = 0.103; r = 0.6, p = 0.065, respectively). Intraperitoneal injection of EMD72000 inhibits orthotopic human pancreatic carcinoma growth in rats. Antiangiogenic effects of anti-EGF-R MAB EMD72000 can be quantified and monitored noninvasively by dynamic MR imaging.