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Jan 08, 2009
 |  BC Innovations  |  Tools & Techniques

Bright idea in cancer

Researchers at the University of Tokyo and the NIH's National Cancer Institute have developed pH-sensitive fluorescent probes that can selectively label viable cancer cells in vivo.1 These probes may be useful as visualization aids in surgery and imaging procedures as well as in drug efficacy studies.

In a paper published in Nature Medicine, researchers described boron-dipyrromethene-based probes conjugated to a mAb targeting cell surface proteins. Following internalization, the conjugated probes become activated only within the acidic microenvironment of lysosomes-a hallmark of viable cells. Damaged or dying cells cannot maintain a low-pH lysosomal microenvironment, and probes within such cells will not activate.

In a proof-of-concept study, a Herceptin-conjugated probe was used to image HER2 (ERBB2)-overexpressing lung metastases in mice. In a second experiment in probe-labeled, tumor-bearing mouse lungs, killing viable cells with pure ethanol significantly lowered relative fluorescence intensity compared with that seen in lung regions labeled with a constitutively active control probe (p<0.0001).

Herceptin trastuzumab, a humanized mAb against HER2 from Genentech Inc. and Roche, is marketed to treat breast cancer.

"There are three issues that arise with whatever you label: you want your label to be specific, you have to wait for the label to accumulate specifically at the target and you have to wait for what doesn't accumulate to wash away," said Jeffrey Peterson, VP of applied biology at VisEn Medical Inc. What Peterson likes about the new technique, he said, is "getting the probe into the cell without having to wait for what doesn't accumulate to wash away. What's circulating is not fluorescent so it shouldn't interfere with your signal."

VisEn markets fluorescence imaging agents and the...

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