title: Real-time optical imaging of primary tumor growth and multiple metastatic events in a pancreatic cancer orthotopic model.
abstract: We report here whole-body optical imaging, in real time, of genetically fluorescent pancreatic tumors growing and metastasizing to multiple sites in live mice. The whole-body optical imaging system is external and noninvasive. Human pancreatic tumor cell lines, BxPC-3 and MiaPaCa-2, were engineered to stably express high-levels of the Aequorea victoria green fluorescent protein (GFP). The GFP-expressing pancreatic tumor cell lines were surgically orthotopically implanted as tissue fragments in the body of the pancreas of nude mice. Whole-body optical images visualized real-time primary tumor growth and formation of metastatic lesions that developed in the spleen, bowel, portal lymph nodes, omentum, and liver. Intravital images in the opened animal confirmed the identity of whole-body images. The whole-body images were used for real-time, quantitative measurement of tumor growth in each of these organs. Intravital imaging was used for quantification of growth of micrometastasis on the liver and stomach. Whole-body imaging was carried out with either a trans-illuminated epi-fluorescence microscope or a fluorescence light box, both with a thermoelectrically cooled color CCD camera. The simple, noninvasive, and highly selective imaging made possible by the strong GFP fluorescence allowed detailed simultaneous quantitative imaging of tumor growth and multiple metastasis formation of pancreatic cancer. The GFP imaging affords unprecedented continuous visual monitoring of malignant growth and spread within intact animals without the need for anesthesia, substrate injection, contrast agents, or restraint of animals required by other imaging methods. The GFP imaging technology presented in this report will facilitate studies of modulators of pancreatic cancer growth, including inhibition by potential chemotherapeutic agents.
authors.affiliation: Department of Surgery, University of California San Diego, San Diego, California 92161, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Bouvet
authors.forename: Jinwei
authors.initials: J
authors.lastname: Wang
authors.forename: Stephanie R
authors.initials: SR
authors.lastname: Nardin
authors.forename: Rounak
authors.initials: R
authors.lastname: Nassirpour
authors.forename: Meng
authors.initials: M
authors.lastname: Yang
authors.forename: Eugene
authors.initials: E
authors.lastname: Baranov
authors.forename: Ping
authors.initials: P
authors.lastname: Jiang
authors.forename: A R
authors.initials: AR
authors.lastname: Moossa
authors.forename: Robert M
authors.initials: RM
authors.lastname: Hoffman
mesh_terms: D000818:Animals; D003952:Diagnostic Imaging; D004195:Disease Models, Animal; D049452:Green Fluorescent Proteins; D006801:Humans; D008164:Luminescent Proteins; D051379:Mice; D008819:Mice, Nude; D008856:Microscopy, Fluorescence; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D010190:Pancreatic Neoplasms / Q000473:pathology* / Q000628:therapy; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
chemical_list: D008164:Luminescent Proteins; D049452:Green Fluorescent Proteins