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J Nucl Med. 2008; 49 (Supplement 1):99P
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Oncology-Basic Science: Basic Science

Correlative Studies

Differentiation of ER{alpha}+ and ER{alpha}-knockdown breast tumors in mice using estrogen receptor PET imaging

Michel Paquette1, René Ouellet1, Etienne Croteau1, Johan Van Lier1, Roger Lecomte1 and François Bénard1

1 Nuclear Medecine and Radiobiology, University of Sherbrooke, Sherbrooke, Quebec, Canada

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Objectives: To develop a non-invasive model in tumor-bearing mice to investigate the use of steroid receptor PET imaging with [18F]fluoroestradiol (FES) as a tool to discriminate between tumors having different ER{alpha} status.

Methods: MC7-L1 and MC4-L2 mouse mammary adenocarcinoma cell lines (ER{alpha}+) received (via lentiviral infection) specific shRNAs against ER{alpha} to create stable ER{alpha}-knockdown cell lines. ER{alpha} status of the infected tumors was confirmed by in vitro assays. An ER{alpha}+ tumor and its ER{alpha}-knockdown counterpart were implanted subcutaneously in the axillary area of Balb-c mice and allowed to grow up to 3 to 5 mm in diameter. Tumor-bearing mice were then scanned with FES using a LabPETTM small animal scanner. A 30-minute static image was acquired one hour post-injection to ensure optimal tumor uptake of the radiotracer. Immediately after, a [18F]FDG PET image was obtained without moving the animal to help define ROIs. Images were reconstructed by MLEM and results determined by the ratio between 4 maximum pixel values in ROIs placed on tumors and the average of pixels in ROIs of non-specific reference tissue.

Results: Western blot analysis showed a significant decrease in ER{alpha} protein content in knockdown cell lines compared to the ER+ cells. In parallel, in vitro pharmacokinetic data obtained using [3H]estradiol showed a 30% decrease of maximum binding in ER{alpha}-knockdown tumors compared with ER+ tumors. ER{alpha}-knockdown tumors have a signal/non-specific tissue value evaluated by FES PET imaging that is {asymp}25% lower than their ER+ equivalent (see Figure), which is similar to in vitro data.

Conclusions: Our preliminary data show that estrogen receptor PET imaging can distinguish differences in ER expression using murine models of hormone sensitive breast cancer.

Research Support: CIHR





This Article
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Right arrow Alert me to new issues of the journal
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Google Scholar
Right arrow Articles by Paquette, M.
Right arrow Articles by Bénard, F.
PubMed
Right arrow Articles by Paquette, M.
Right arrow Articles by Bénard, F.