NON INVASIVE LONGITUDINAL ASSESSMENT OF TUMOR GROWTH BY MRI AND BIOLUMINESCENCE IMAGING IN EXPERIMENTAL MODELS OF PANCREATIC AND RECTAL CANCER

Background: Pancreatic cancer is one of the most lethal human cancers with an overall survival rate of 3-5 % and a median survival of less than 6 months. Colorectal cancer is the third most common cancer diagnosed; and it’s the second leading cause of cancer related death in the United States. To date an effective system is strongly needed which accurately predict the clinical efficacy of new compounds developed in oncology for pancreatic cancer, and colorectal cancer. Aims: The aim of the current study is to contribute: To the time dependent evolution of both pancreatic and colorectal. In the second case we also evaluated the performance of BLI and MRI for the differentiation of normal to metastatic lymph nodes. Methods: Human pancreatic cancer cells (PANC-1-Luc+) were injected into the pancreas of female athymic CD1 mice. Bioluminescence (BLI) and Magnetic Resonance Images (MRI) were acquired in each mouse at three time points after cell inoculation (1, 2 and 3 months). Two groups of mice were studied: the first group of n=13 mice in which 5*106 cells were injected and the second group of n=10 mice in which 2*106 cells were injected. MRI examinations included T2w acquisitions and (at the last time point) Dynamic-contrast-enhanced-MRI (DCE-MRI). Human colorectal cancer cells (ht-29) ht-29_luc cancer cells were injected into the submucosal layer of the rectum by transanal microinjection. BLI and MRI were acquired in each mouse at three time points (1,2,3 weeks) for the in vivo evaluation of tumor growth, lymph nodes involvement and metastasis formation. At last time point after MRI and BLI imaging acquisition, for the purpose of ex vivo study of lymph nodes metastasis. Mice were sacrificed and the abdominal cavity exposed, two iliac LN were then excised for each animal in experiment for a total of ten lymph nodes. RESULTS: - In the pancreatic cancer study, mice underwent three MRI and BLI examinations without mortality. BLI was more sensitive than MRI producing higher detection rate at early time points. Moreover in one case of abdominal dissemination of pancreatic tumor cells, small tumor masses were detected by BLI and not detected by MRI. In 4 mice BLI produced false negative results. DCE-MRI experiments providing information on tumor perfusion were conducted successfully in this anatomical district. Results for colorectal study demonstrated that: BLI and MRI were able to detect the presence and localization of the primary lesions and to access its progression. A positive linear correlation was obtained between MRI and BLI tumor volume. Lymph nodes were visible only in MRI, but no differentiation between positive and negative lymph nodes was detected in images. Since the BLI modality was not able to detect the lymph nodes in vivo, we undertook the ex-vivo iliac lymph nodes excision of five animals. Ex vivo BLI images indicate that 70% of iliac nodes developed metastasis. Conclusions: The present study performed on the experimental model of pancreatic cancer and colorectal cancer, shows that MRI and BLI are complementary techniques and that synergistic application of both can overcome the intrinsic limitations of each.