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

Breast Cancer Research

Ekaterina Dadachova³  Jeffrey W Pollard¹  M Donald Blaufox³  Joseph Mani³  Ping Lu³  Elaine Y Lin¹  Andrew V Nguyen²  Renee M Moadel³ 

[1] Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, New York, USA;Department of Microbiology and Immunology, Albert Einstein College of Medicine of Yeshiva University, Bronx, New York, USA;Department of Nuclear Medicine, Albert Einstein College of Medicine of Yeshiva University, Bronx, New York, USA

关键词: therapy;    positrons;    mouse models;    2-deoxy-2-[¹⁸F]fluoro-D-glucose;    breast cancer;   

Others  :  1118790
DOI  :  10.1186/bcr643

 received in 2003-04-08, accepted in 2003-07-17,  发布年份 2003

【 摘 要 】

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.

【 授权许可】

   
2003 Moadel et al., licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL.

【 图 表 】

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