Gene that allows fireflies to flash is helping researchers track the effectiveness of anti-cancer drugs

Researchers at UT Southwestern Medical Centre, US, are among the first to show that a technique called bioluminescence imaging (BLI) can be used to determine the effectiveness of cancer drugs that choke a tumour's blood supply.

The technique requires a substrate called luciferin to be added to the bloodstream, which carries it to cells throughout the body. When luciferin reaches cells that have been altered to carry the firefly gene, those cells emit light.

Some cancer drugs, however, work by cutting off the blood supply to tumour cells. Given that luciferin is delivered via the vasculature, the researchers set out to determine the kinetics of luciferin delivery and whether BLI techniques could be used to gauge the effectiveness of drugs that destroy blood vessels feeding tumours.

They tested their theory in mice bearing human breast-cancer tumours. Before being introduced to the animals, the tumour 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.

The researchers monitored light emissions from the tumours following administration of the luciferin. The mice didn't visibly glow; special light-detecting equipment was used to observe strong correlations between the amount of light emitted and the size of the tumour as it grew. Detected light emission, however, 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," said Dr. Ralph Mason, professor of radiology, director of the UT Southwestern Cancer Imaging Center and senior author of the study. "The technique is not intended to be used for imaging tumours or diagnosing cancer in humans, but it potentially allows us to do much more efficient pre-clinical experiments."

Dr. Mason stressed that light-emission kinetics depend heavily on tumour location.

The findings are available online and in a future issue of the Journal of the Federation of American Societies for Experimental Biology.

Although magnetic resonance imaging (MRI) remains the gold standard of medical imaging, BLI has its advantages. The non-invasive procedure allows detection of cell viability not accessible by MRI and is less costly, according to researchers at UT Southwestern.

"Ultimately, the MRI is much more sophisticated and can do more, but BLI is very straight-forward," Dr. Mason said. "It's perfect for evaluating new classes of drugs designed to cause acute vascular changes in tumours because the tests are inexpensive and easy to do."

Dr. Mason said it's critically important to develop new chemotherapeutic drugs because existing therapies, when used on their own, are far from ideal. "We're lacking the optimal drugs as demonstrated by the people who are not cured by chemotherapy," he said.

He said many existing drugs kill 99 percent of a tumour but allow a few cells to survive, giving the tumour an opportunity 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," he said. "BLI provides an opportunity to do those tests cheaply and efficiently."

Dr. Mason said a handful of faculty members spent several months and about $50,000 to build the BLI instrument they used to collect this data. The team needed the charge-coupled device to detect the light emitted by the cancer cells because the light is too weak for human eye