Predicting Cancer Drugs' Impact

New imaging probes show whether cancer drugs will work.

Devising the right chemotherapy regimen as soon as possible can spare cancer patients from painful side effects and increase their chances of survival. Two new imaging contrast agents could help by showing doctors whether a drug will reach the target tumor before it is administered.

Go for the jugular: A new imaging probe accumulates in leaky tumor blood vessels, just like the drug doxil, and helps researchers predict whether the drug will work. This fluorescence-microscopy image shows a tumor removed from a mouse that was treated with the imaging agent, which is labeled red. Credit: Radiology

The first imaging agent can be used in combination with mammography to show doctors how well a commonly used breast-cancer drug will work, by quantifying the leakiness of a tumor's blood supply. The imaging probe has been used to determine whether the drug will work in mice, and it's on its way to clinical trials in humans.

Developed by Ravi Bellamkonda, a professor of bioengineering at Georgia Tech, and his colleagues, the imaging method is one of the first of its kind. The agent can be used to predict the effectiveness of a drug that has been one of nanomedicine's early success stories. Marketed under the name doxil, it is a DNA-disrupting molecule encapsulated within a large lipid-and-polymer envelope. The envelope bulks up the drug to such a size that it cannot exit the blood stream and enter healthy organs, preventing side effects including liver and heart damage. But the drug can still get inside many tumors because their blood vessels are misshapen and leaky. The drug is currently used to treat several cancer types, including those of the breast and ovaries, but how well it works hinges on whether a tumor has enough leaky blood vessels to let it in.

"Though tumor sizes might be the same, the leakiness is all over the place," says Bellamkonda. For a few years now, his lab has been using liposomes carrying iodine, which acts as a contrast agent, to image both tumor and healthy blood vessels. The liposomes are used with any imaging technique that relies on x-rays, including mammography and CT scans. Since the size and chemistry of the liposomes are similar to those of doxil and other lipid-enveloped drugs, Bellamkonda suspected that the imaging agents might interact with tumors in a similar way.

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In a study published in this month's issue of the journal Radiology, Bellamkonda's research group describes using this contrast agent to quantify breast-cancer blood-vessel leakiness in mice. This, in turn, allowed the researchers to predict how successful doxil treatment would be. "We can predict if the drug will or won't get there," he says. Based on these predictions, the Georgia Tech researchers correctly predicted whether administering the drug would significantly shrink breast-cancer tumors in the mice.

It remains to be seen whether Bellamkonda's imaging agent can help predict efficacy of other therapies, because many existing cancer drugs are smaller than the liposome particles. However, the bulky encapsulation used to make doxil is being developed for other cancer drugs.