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Watching cancer cells die

Mar 2010
Marie Freebody,

Imagine being able to monitor the effectiveness of a cancer treatment cheaply, easily and, most importantly, without harm to the patient undergoing therapy. That’s exactly what researchers at the University of Notre Dame are hoping will one day be possible, thanks to their pioneering work using a synthetic near-infrared fluorophore that targets dead and dying cells.

The ability to evaluate the efficacy of cancer treatments in living patients is almost as important as the cancer therapy itself. The Notre Dame group has successfully demonstrated whole-body optical imaging using a small synthetic fluorescent probe localized specifically to the dead and dying cells inside prostate and mammary tumors in rats and mice. They believe that the probe’s capacity to target cell death in different tumor models suggests that it could be universally used to detect cell death.

Lead author Bryan Smith conducts fluorescence imaging of animals with implanted tumors using the Kodak Multispectral imaging station. Images courtesy of the University of Notre Dame.

“Our probe will help biomedical studies of cell death by allowing researchers to follow the occurrence of cell death in a living animal,” said Bradley Smith, a researcher at the university. “Using our probe, it should be possible to develop imaging methods that monitor the efficacy of cancer therapy in animal models, thus facilitating anticancer research.”

Eventually, it may be possible to develop imaging methods that evaluate the efficacy of cancer therapy in individual human patients. What is more, the probe also may be applied to other disease processes where cell death plays an important role, such as atherosclerosis, ischemia, allograft rejection and neurodegenerative disorders.

Today, a number of methods are commonly employed to image tumors in living animals, including optical, MRI, PET and radionuclide imaging. Historically, tumor imaging has focused on radionuclide or PET imaging because of their direct clinical application.

The drawback to radionuclide imaging is that it is very expensive, requiring highly specialized equipment, trained personnel and radiolabels. Furthermore, radionuclide imaging uses ionizing energy, which poses harm to both the researcher and the animal, limiting the number of time points in a study.

On the other hand, the new near-infrared fluorescence optical imaging technique does not involve ionizing radiation or radiolabels, making it safer and cheaper than radionuclide imaging. Details of the method were published online in the Journal of the American Chemical Society in December 2009.

A fluorescence intensity image of a targeted prostate tumor in a rat model is shown, overlaid on the corresponding x-ray. Insert shows highest fluorescence intensity at the tumor core. Courtesy of the American Chemical Society.

Tumors often have high amounts of cell death, a fact that lies at the heart of the researchers’ technique. The team developed a series of small synthetic probe molecules with an attached near-infrared dye that target a particular molecule, known as phosphatidylserine, typically found at the surface of dying cells.

In the experiments, cancer cells are injected underneath the skin on the flank of a living animal and left to grow for 14 days. The tumor-bearing animals are then injected intravenously with 3 mg/kg of the near-infrared fluorescent probe. Finally, a Kodak Multispectral imaging station is used to image the animal every few hours.

Future studies will evaluate whether tumor cell death can be monitored in a living animal undergoing various anticancer treatments. “Eventually, we would like to replace the fluorophore with a radionuclide or PET label so our probe can be used to image cell death in deeper tissues,” Smith said. “This would lead to imaging applications in humans, but this is a few years away.”

allograft rejectionanticancer researchatherosclerosisBiophotonicsBioScanBradley SmithimagingischemiaJournal of the American Chemical SocietyKodak Multispectral imaging stationmammary tumorMarie FreebodyMRInear-infrared fluorophoreneurodegenerative disordersNewsopticsPETphosphatidylserineprostate tumorradionuclide imagingSmithUniversity of Notre Dame

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