Whole-body optical imaging of green fluorescent protein-expressing tumors and metastases.

Abstract

We have imaged, in real time, fluorescent tumors growing and metastasizing in live mice. The whole-body optical imaging system is external and noninvasive. It affords unprecedented continuous visual monitoring of malignant growth and spread within intact animals. We have established new human and rodent tumors that stably express very high levels of the Aequorea victoria green fluorescent protein (GFP) and transplanted these to appropriate animals. B16F0-GFP mouse melanoma cells were injected into the tail vein or portal vein of 6-week-old C57BL/6 and nude mice. Whole-body optical images showed metastatic lesions in the brain, liver, and bone of B16F0-GFP that were used for real time, quantitative measurement of tumor growth in each of these organs. The AC3488-GFP human colon cancer was surgically implanted orthotopically into nude mice. Whole-body optical images showed, in real time, growth of the primary colon tumor and its metastatic lesions in the liver and skeleton. Imaging was with either a trans-illuminated epifluorescence microscope or a fluorescence light box and thermoelectrically cooled color charge-coupled device camera. The depth to which metastasis and micrometastasis could be imaged depended on their size. A 60-microm diameter tumor was detectable at a depth of 0.5 mm whereas a 1, 800-microm tumor could be visualized at 2.2-mm depth. The simple, noninvasive, and highly selective imaging of growing tumors, made possible by strong GFP fluorescence, enables the detailed imaging of tumor growth and metastasis formation. This should facilitate studies of modulators of cancer growth including inhibition by potential chemotherapeutic agents.

• Authors: M Yang, E Baranov, P Jiang, F X Sun, X M Li, L Li, S Hasegawa, M Bouvet, M Al-Tuwaijri, T Chishima, H Shimada, A R Moossa, S Penman, R M Hoffman
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 97 Issue 3 Pg. 1206-11 (Feb 01 2000) ISSN: 0027-8424 [Print] United States
• PMID: 10655509 (Publication Type: Journal Article)

Chemical References

• Luminescent Proteins
• Recombinant Fusion Proteins
• Green Fluorescent Proteins

Topics

• Adenocarcinoma (genetics, metabolism, pathology, secondary)
• Animals
• Bone Neoplasms (pathology, secondary)
• Brain Neoplasms (pathology, secondary)
• Colonic Neoplasms (genetics, metabolism, pathology)
• Diagnostic Imaging (methods)
• Female
• Green Fluorescent Proteins
• Liver Neoplasms (pathology, secondary)
• Luminescent Proteins (analysis, genetics)
• Male
• Melanoma, Experimental (genetics, metabolism, pathology, secondary)
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Mice, Nude
• Microscopy, Fluorescence
• Neoplasm Metastasis (diagnosis)
• Neoplasm Transplantation
• Recombinant Fusion Proteins (analysis, genetics)