A gene that can produce a flash in fireflies has been used to track the effectiveness of anti-cancer drugs by researchers at UT Southwestern Medical Center.
In a first of its kind effort, researchers have now shown that a technique called bioluminescence imaging (BLI) can be used to determine the effectiveness of cancer drugs that obstruct the blood supply to a tumor.
AdvertisementIn this technique, the scientists make use of a substrate called luciferin to be added to the bloodstream, which carries it to cells throughout the body. When luciferin reaches the cells that have been altered to carry the firefly gene, these cells are found to emit light. However, there are a few cancer drugs, which work by cutting off the blood supply to tumor cells.
As we know that luciferin is delivered via the vasculature, the researchers wanted to find out the kinetics of luciferin delivery and if BLI techniques could be used to gauge the effectiveness of drugs that destroy blood vessels that feed tumors.
The researchers tested the theory in mice bearing human breast-cancer tumors. Before being introduced to the animals, the tumor cells had been transfected with the firefly gene, which becomes part of the cells as they divide and grow just like genetically modified, herbicide-resistant food crops.
For carrying out the study, firstly BLI was used to monitor light emissions from tumors, followed by administration of the luciferin. As the mice didn't visibly glow, the researchers resorted to special light-detecting equipment for observing strong correlations between the amount of light emitted and the size of the tumor as it grew. However, the detected light emission was severely reduced after the vascular-disrupting drug was administered.
"What we've done is offer proof-of-concept that BLI may be an effective and cheaper method to assess drug development and effectiveness. The technique is not intended to be used for imaging tumors or diagnosing cancer in humans, but it potentially allows us to do much more efficient pre-clinical experiments," said Dr. Ralph Mason, professor of radiology, director of the UT Southwestern Cancer Imaging Center and senior author of the study.
Mason highlighted that light-emission kinetics depend heavily on tumor location. Also, BLI has its advantages over the classic magnetic resonance imaging (MRI).
He further said that it's time to initiate development of new chemotherapeutic drugs because existing therapies, when used on their own, are not up to the mark.
"We're lacking the optimal drugs as demonstrated by the people who are not cured by chemotherapy," he said.
He added that a number of existing drugs kill 99 percent of a tumor but still allow a few cells to survive, making it possible for the tumor to grow back.
"Therefore, you need to do a lot of tests to optimize dosing, optimize repeat delivery and probably optimize the co-administration of other, more traditional drugs or therapies. BLI provides an opportunity to do those tests cheaply and efficiently," he said.
Mason said BLI instrument they used to collect this data is essentially an astronomy kit.
"When you're looking at the stars, you're trying to assess very weak light signals. We're using the same type of instrument to access very weak light coming out of an animal. The difference is that here, we have a very sensitive camera instead of a telescope," he said.
The findings are available online and in a future issue of the Journal of the Federation of American Societies for Experimental Biology.
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