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Optical imaging of blood vessel formation in live mice
New model for testing angiogenesis inhibitors
By Bijal P. Trivedi

Scientists have developed a new system for cheaply and easily monitoring tumor and blood vessel growth in live mice over time. Blood vessel formation, or angiogenesis, is crucial for the growth and metastasis of tumors, which makes the process a promising target for anti-cancer drugs.

Robert Hoffman, of AntiCancer, Inc, in San Diego, CA, and colleagues have engineered human tumor cells to express a jellyfish gene that produces a bright green fluorescent protein called GFP. When these tumors are implanted in the mouse footpad or breast fat, the tumors glow bright enough to be seen through the skin. The growth of blood vessels is easily monitored because the mouse's dark blood vessels contrast with the brightly glowing green tumor mass; the contrast of vessel against tumor is like bare tree branches against winter sky.

The contrast was so great, in fact, that the number and length of new blood vessels could be determined without any invasive procedures. Hoffman's team added the GFP gene to human breast, lung, pancreatic, and prostate cancer cells, and implanted each type of tumor into clinically equivalent locations in the mouse. The breast and lung tumor cells were implanted into the breast fat and footpad, respectively. The mice were placed under a blue light, which excites the GFP and makes it glow, and then imaged every few days.

When the prostate and pancreatic tumors were implanted, the scientists used intravital imaging—the animals were opened up, placed under the blue light and photographed.

Previous methods required that the animal be sacrificed, in order to remove the tumor and prepare it for analysis. This prevented scientists from directly observing angiogenesis, or the effects of angiogenesis inhibitors, in vivo, over time.

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Yang, M. et al. Whole-body and intravital optical imaging of angiogenesis in orthotopically implanted tumors. Proc Natl Acad Sci USA 98, 2616-2621 (February 27, 2001).

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