Positron emission tomography agent 2-deoxy-2-[18F]fluoro-D-glucose has a therapeutic potential in breast cancer.

Renee M. Moadel, Andrew V. Nguyen, Elaine Lin, Ping Lu, Joseph Mani, M. Donald Blaufox, Jeffrey W. Pollard, Ekaterina Dadachova

Research output: Contribution to journalArticle

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Abstract

BACKGROUND: Novel approaches are needed for breast cancer patients in whom standard therapy is not effective. 2-Deoxy-2-[18F]fluoro-D-glucose (18F-FDG) was evaluated as a potential radiomolecular therapy agent in breast cancer animal models and, retrospectively, in patients with metastatic breast cancer. METHODS: Polyoma middle T antigen (PyMT) and mouse mammary tumor virus-NeuT transgenic mice with tumors 0.5-1 cm in diameter were imaged with 18F-FDG, and tumor to liver ratios (TLRs) were calculated. The radiotoxicity of 18F-FDG administration was determined in healthy mice. PyMT mice with small (0.15-0.17 cm) and large (more than 1 cm) tumors were treated with 2-4 mCi of 18F-FDG, and control C3H/B6 mice with 3 mCi of 18F-FDG. At 10 days after treatment the tumors and control mammary glands were analyzed for the presence of apoptotic and necrotic cells. Five patients with breast cancer and metastatic disease were evaluated and standardized uptake values (SUVs) in tumors, maximum tolerated dose, and the doses to the tumor were calculated. RESULTS: Doses up to 5 mCi proved to be non-radiotoxic to normal organs. The 18F-FDG uptake in mouse tumors showed an average TLR of 1.6. The treatment of mice resulted in apoptotic cell death in the small tumors. Cell death through the necrotic pathway was seen in large tumors, and was accompanied by tumor fragmentation and infiltration with leukocytes. Normal mammary tissues were not damaged. A human 18F-FDG dose delivering 200 rad to the red marrow (less than 5% damage) was calculated to be 4.76 Ci for a 70 kg woman, and the dose to the tumors was calculated to be 220, 1100 and 2200 rad for SUVs of 1, 5 and 10, respectively. CONCLUSION: We have shown that positrons delivered by 18F-FDG to mammary tumors have a tumoricidal effect on cancer cells. The study of breast cancer patients suggests that the tumor and normal organ dosimetry of 18F-FDG makes it suitable for therapy of this malignancy.

Original languageEnglish (US)
JournalBreast cancer research : BCR
Volume5
Issue number6
StatePublished - 2003
Externally publishedYes

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Fluorodeoxyglucose F18
Positron-Emission Tomography
Breast Neoplasms
Neoplasms
Glucose
Therapeutics
Viral Tumor Antigens
Cell Death
Mouse mammary tumor virus
Maximum Tolerated Dose
Inbred C3H Mouse
Liver
Human Mammary Glands
Transgenic Mice
Breast
Leukocytes
Animal Models

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Moadel, R. M., Nguyen, A. V., Lin, E., Lu, P., Mani, J., Blaufox, M. D., ... Dadachova, E. (2003). Positron emission tomography agent 2-deoxy-2-[18F]fluoro-D-glucose has a therapeutic potential in breast cancer. Breast cancer research : BCR, 5(6).

Positron emission tomography agent 2-deoxy-2-[18F]fluoro-D-glucose has a therapeutic potential in breast cancer. / Moadel, Renee M.; Nguyen, Andrew V.; Lin, Elaine; Lu, Ping; Mani, Joseph; Blaufox, M. Donald; Pollard, Jeffrey W.; Dadachova, Ekaterina.

In: Breast cancer research : BCR, Vol. 5, No. 6, 2003.

Research output: Contribution to journalArticle

Moadel, RM, Nguyen, AV, Lin, E, Lu, P, Mani, J, Blaufox, MD, Pollard, JW & Dadachova, E 2003, 'Positron emission tomography agent 2-deoxy-2-[18F]fluoro-D-glucose has a therapeutic potential in breast cancer.', Breast cancer research : BCR, vol. 5, no. 6.
Moadel, Renee M. ; Nguyen, Andrew V. ; Lin, Elaine ; Lu, Ping ; Mani, Joseph ; Blaufox, M. Donald ; Pollard, Jeffrey W. ; Dadachova, Ekaterina. / Positron emission tomography agent 2-deoxy-2-[18F]fluoro-D-glucose has a therapeutic potential in breast cancer. In: Breast cancer research : BCR. 2003 ; Vol. 5, No. 6.
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abstract = "BACKGROUND: Novel approaches are needed for breast cancer patients in whom standard therapy is not effective. 2-Deoxy-2-[18F]fluoro-D-glucose (18F-FDG) was evaluated as a potential radiomolecular therapy agent in breast cancer animal models and, retrospectively, in patients with metastatic breast cancer. METHODS: Polyoma middle T antigen (PyMT) and mouse mammary tumor virus-NeuT transgenic mice with tumors 0.5-1 cm in diameter were imaged with 18F-FDG, and tumor to liver ratios (TLRs) were calculated. The radiotoxicity of 18F-FDG administration was determined in healthy mice. PyMT mice with small (0.15-0.17 cm) and large (more than 1 cm) tumors were treated with 2-4 mCi of 18F-FDG, and control C3H/B6 mice with 3 mCi of 18F-FDG. At 10 days after treatment the tumors and control mammary glands were analyzed for the presence of apoptotic and necrotic cells. Five patients with breast cancer and metastatic disease were evaluated and standardized uptake values (SUVs) in tumors, maximum tolerated dose, and the doses to the tumor were calculated. RESULTS: Doses up to 5 mCi proved to be non-radiotoxic to normal organs. The 18F-FDG uptake in mouse tumors showed an average TLR of 1.6. The treatment of mice resulted in apoptotic cell death in the small tumors. Cell death through the necrotic pathway was seen in large tumors, and was accompanied by tumor fragmentation and infiltration with leukocytes. Normal mammary tissues were not damaged. A human 18F-FDG dose delivering 200 rad to the red marrow (less than 5{\%} damage) was calculated to be 4.76 Ci for a 70 kg woman, and the dose to the tumors was calculated to be 220, 1100 and 2200 rad for SUVs of 1, 5 and 10, respectively. CONCLUSION: We have shown that positrons delivered by 18F-FDG to mammary tumors have a tumoricidal effect on cancer cells. The study of breast cancer patients suggests that the tumor and normal organ dosimetry of 18F-FDG makes it suitable for therapy of this malignancy.",
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AU - Nguyen, Andrew V.

AU - Lin, Elaine

AU - Lu, Ping

AU - Mani, Joseph

AU - Blaufox, M. Donald

AU - Pollard, Jeffrey W.

AU - Dadachova, Ekaterina

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N2 - BACKGROUND: Novel approaches are needed for breast cancer patients in whom standard therapy is not effective. 2-Deoxy-2-[18F]fluoro-D-glucose (18F-FDG) was evaluated as a potential radiomolecular therapy agent in breast cancer animal models and, retrospectively, in patients with metastatic breast cancer. METHODS: Polyoma middle T antigen (PyMT) and mouse mammary tumor virus-NeuT transgenic mice with tumors 0.5-1 cm in diameter were imaged with 18F-FDG, and tumor to liver ratios (TLRs) were calculated. The radiotoxicity of 18F-FDG administration was determined in healthy mice. PyMT mice with small (0.15-0.17 cm) and large (more than 1 cm) tumors were treated with 2-4 mCi of 18F-FDG, and control C3H/B6 mice with 3 mCi of 18F-FDG. At 10 days after treatment the tumors and control mammary glands were analyzed for the presence of apoptotic and necrotic cells. Five patients with breast cancer and metastatic disease were evaluated and standardized uptake values (SUVs) in tumors, maximum tolerated dose, and the doses to the tumor were calculated. RESULTS: Doses up to 5 mCi proved to be non-radiotoxic to normal organs. The 18F-FDG uptake in mouse tumors showed an average TLR of 1.6. The treatment of mice resulted in apoptotic cell death in the small tumors. Cell death through the necrotic pathway was seen in large tumors, and was accompanied by tumor fragmentation and infiltration with leukocytes. Normal mammary tissues were not damaged. A human 18F-FDG dose delivering 200 rad to the red marrow (less than 5% damage) was calculated to be 4.76 Ci for a 70 kg woman, and the dose to the tumors was calculated to be 220, 1100 and 2200 rad for SUVs of 1, 5 and 10, respectively. CONCLUSION: We have shown that positrons delivered by 18F-FDG to mammary tumors have a tumoricidal effect on cancer cells. The study of breast cancer patients suggests that the tumor and normal organ dosimetry of 18F-FDG makes it suitable for therapy of this malignancy.

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