Radioactive glucose kills breast cancer cells

The radioactive glucose widely used in positron emission tomography exerts a tumoricidal effect on breast cancer cells in mice and represents a potential new therapy for metastatic breast cancer.

The rate of glucose utilization is enhanced in neoplastic cells, Dr. Ekaterina Dadachova and colleagues explain in Breast Cancer Research, published online on August 22. Because this agent, 2-deoxy-2-[F-18]fluoro-D-glucose (F-18-FDG), is not a substrate for glycolysis, it remains trapped in the cell. Positrons have a half-life of 110 minutes and path length in tissue of about 0.1 to 0.2 cm.To test F-18-FDG as a potential radiomolecular therapeutic agent, the researchers at Albert Einstein College of Medicine in the Bronx, New York, used transgenic mice that grow mammary tumors. Tumor uptake of F-18-FDG was uniform.In healthy mice, radioactivity was undetectable 24 hours after injection of F-18-FDG. Treatment with doses of up to 5 mCi F-18-FDG caused no damage in major organs of healthy mice after 4 weeks of observation.In 10-week old transgenic mice that developed mammary tumors of approximately 0.16 cm in diameter, 4% of tumor cells were apoptotic 10 days after treatment. Apoptosis was detected in less than 1% of tumors in untreated animals.Necrosis was dominant over apoptosis in larger tumors of 22-week old mice, encompassing 14% of the tumors greater than 1 cm.Dr. Dadachova’s group then retrospectively evaluated F-18-FDG scans of five patients with metastatic breast cancer. Standardized uptake values were uniform within tumors at F-18-FDG doses estimated to be tumoricidal, the report indicates. Uptake increased as tumor size increased.The researchers point out that radiotoxicity to normal tissue can be reduced by fasting, diuresis, administration of small doses of F-18-FDG over time, and administration of corticosteroids. In an interview with Reuters Health, Dr. Dadachova noted that her team has also demonstrated prolonged survival in tumor-bearing mice treated with F-18-FDG.”Any tumors that metabolize glucose at a higher rate than normal tissue, such as neuronomas and colon cancers,” are candidates for F-18-FDG and other positron-labeled agents, Dr. Dadachova added. However, she expects that positron treatment will be reserved for patients who fail first-line therapy.Dr. Dadachova and her associates plan to submit a proposal to their institutional review board to start phase I clinical trials in about 6 months.(Source: Breast Cancer Res 2003;5:R199-R205: Reuters Health: Karla Gale: August 26, 2003: Oncolink)