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Fluorescent cancer cells to guide brain surgeons

Malignant brain tumours grow with fine extensions which make them hard to distinguish from healthy brain tissue during surgery. Scientists of the German Cancer Research Centre (Deutsches Krebsforschungszentrum) and the University of Heidelberg have developed a staining method that makes tumour cells glow in yellow-green. Thus, borders between tumour tissue and normal tissue become visible during the entire operation, which makes resection easier for brain surgeons.

Dr. Eva Frei © German Cancer Research Centre

Gliomas are malignant brain tumours that arise from glial (supporting) cells of the brain. Gliomas are often resistant to chemotherapy. These tumours grow fine extensions that infiltrate normal brain tissue and, in addition, individual tumour cells can form satellites in surrounding tissue. Therefore, it is almost impossible to remove the tumour tissue completely by surgery.

Yet, radical surgical removal of the tumour would substantially improve the prognosis of patients. Surgeons are confronted with the difficulty of discriminating between tumour tissue and healthy brain tissue during surgery. Dr. Eva Frei of the DKFZ, collaborating with doctors and researchers of the Medical Faculty of Heidelberg University, has now developed a method to improve neurosurgery.

The scientists took advantage of the fact that tumours cover their increased energy needs, among other things, by taking up large amounts of the blood protein albumin. The researchers attached a fluorescent substance (5-aminofluorescein) to albumin, which is distributed throughout the body via the bloodstream and eventually accumulates in the brain tumor. Laser light causes the substance to glow and makes the fine extensions of the tumour visible.

"Other contrast agents often fade," says Dr. Eva Frei, "for tumour resection can take five to six hours." The fluorescence marker attached to albumin, however, is visible during the entire operation.

The scientists tested the albumin method in thirteen patients with malignant gliomas. In nine cases it was possible to remove the fluorescent tumor tissue completely thanks to the intensive yellow-green light signal. The researchers calculated that the probability of the glowing tissue being tumor cells is 97 percent.

“Staining is a tremendous help for the surgeon, because he or she can recognize the exact borders between tumor and normal brain tissue, which is normally very difficult,” explains Eva Frei. “Another problem is that the tumour often exerts pressure on the meninx so that, when it is opened for surgery, the tumour shifts or changes its shape.” The new method takes account of this ‘brain shift’ effect and makes the effort of intraoperative MRI unnecessary. Further advantages of the new method are that it is tolerable, inexpensive and easy to apply.

Tolerability and effectiveness of the staining method will be validated next year in a larger study involving several hospitals. The scientists will monitor in a long-term study whether the prognosis of patients will improve as a result of the new method.

Original publication:

Paul Kremer, Mahmoudreza Fardanesh, Reinhard Ding, Maria Pritsch, Saida Zoubaa and Eva Frei: Intraoperative fluorescence staining of malignant brain tumors using 5-aminofluorescein-labeled albumin. Neurosurgery 2009, DOI:10.1227/01.NEU.0000335787.17029.67.

Website address: https://www.gesundheitsindustrie-bw.de/en/article/press-release/fluorescent-cancer-cells-to-guide-brain-surgeons