Abstract

Abstract Colorectal cancer is one of the most common malignant diseases in the world, and its prognosis is generally poor. Liver metastases of colorectal cancer significantly affect the fates of patients. To further understand the pathological aspects of distant metastases, we have established liver metastasis models of human colon cancer xenografts in immune-deficient NOD/Shi-scid/IL-2Rγnull (NOG) mice. 18F-fluorodeoxyglucose positron emission tomography / x-ray computed tomography (18F-FDG-PET/CT) is useful in the clinical evaluation of various human cancers. While PET analysis was established to evaluate subcutaneous lesions of human cancer xenografts in mice, its application to internal lesions including liver metastases is still being developed. We applied PET approaches for the evaluation of in vivo metastatic lesions in the internal organs of living small experimental animals. In this study, we analyzed in vivo liver metastases of human colon cancer cell lines in NOG mice using PET imaging. Experimental liver metastases were established by intrasplenic injection of human colon cancer cell line HCT116 (1.0 x 105 or 1.0 x 106 cells/mouse). 18F-FDG-PET/CT scans were performed 2 weeks after xeno-transplantation. After PET/CT scans, histopathological examinations were also performed to precisely confirm lesions. 18F-FDG-PET/CT imaging clearly demonstrated multiple hot spots on livers in spite of disadvantages in the contrast between tumor soft tissues and markedly swollen livers. PET/CT analysis also disclosed increased standardized uptake values (SUV) of FDG in metastatic foci of NOG mice (control, SUVmean 0.450 ± 0.033, SUVmax 0.635 ± 0.017; 1.0 x 105 cells, 0.853 ± 0.087, 1.254 ± 0.237; 1.0 x 106 cells, 1.211 ± 0.108, 1.701 ± 0.158). There were significant differences in FDG uptakes between the three groups (ANOVA, p=0.017 in SUVmean, p=0.044 in SUVmax, n=2). We clearly and quantitatively detected liver metastasis images in NOG mice by 18F-FDG-PET/CT in vivo. Immunohistochemical examinations confirmed more metastatic foci and more severe hepatomegaly with 1.0 x 106 than 1.0 x 105 of HTC116 cell inoculations. PET/CT analysis of human cancer xenografts is a new and reliable system to evaluate metastatic lesions in internal organs. In conclusion, this model system is useful for analyzing metastatic mechanisms and developing new therapeutic approaches for the liver metastatic lesions of human cancer. Citation Format: Tsuyoshi Chijiwa, Kenji Kawai, Hideo Tsukada, Hiroshi Suemizu, Masato Nakamura. 18F-FDG-PET/CT imaging analyses for liver metastases of human colon cancer xenografts in NOG mice. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2675. doi:10.1158/1538-7445.AM2013-2675

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