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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 Acqurea 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 imaging was used for quatification 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
fluorescent 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 unprecendented contionuous
visual monitoring of malignant growth and spread within intact animals
without the need for anesthesia, substrate injection, control agents, or
restraint of animals required by the 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.
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The human pancreatic tumor cell line, BxPC-3, was engineered to stably express high-levels of the Aquorea victoria green fluorescent protein (GFP). The GFP-expressing pancreatic tumor cell line was surgically orthotopically implanted (SOI) as tissue fragments in the body of the pancreas of nude mice. Intravital imaging was used for quantification of growth metastasis on the liver. The diameters of the three micrometastases were 288 mm and 208 mm the right lobe and 344 mm on the left lobe as quantified by image analysis at day-70 post SOI. |