ZR-75-1 breast cancer models to study the utility of (18)F-FES by PET imaging

BACKGROUND: Breast cancer is a hormone-dependent tumor, and 70–80% of breast cancer patients are estrogen receptor (ER) positive. ZR-75-1 cell lines are more consistent with human breast cancer, which is mostly ER positive and PR positive. To better study the biological characteristics of (18)F-fluoroestradiol ((18)F-FES) in breast cancer patients, ZR-75-1 breast cancer models were selected to provide a basis for further clinical application. METHODS: (18)F-FES uptake in vivo was evaluated in ZR-75-1 tumor-bearing mice, using MCF-7 tumor-bearing mice as a positive control. Competitive inhibition experiment was also performed, using ER down-regulator fulvestrant. Biodistribution of (18)F-FES was observed in ZR-75-1 breast tumor-bearing mice scanning by (18)F-FES-PET/CT in vivo and γ counter ex vivo. The expression of ER was also determined by immunohistochemistry. An abnormal toxicity test was performed in ICR male mice whose behavior and vital signs were observed within 48 hours of (18)F-FES injection. OLINDA/EXM 2.0 software was used to calculate the absorbed doses of adult female body phantoms. RESULTS: There was no significant difference in FES uptake between ZR-75-1 and MCF-7 tumor-bearing mice. Intervention with fulvestrant decreased the uptake of (18)F-FES. Biodistribution studies demonstrated that the uptake of (18)F-FES was high in the liver and kidneys but low in the brain. Other than excretory organs, the uptake of (18)F-FES in ER-positive breast tumors was significantly higher than in ER-negative tissues. The estimated human effective dose was 0.016 mSv/MBq for the adult female body model. CONCLUSIONS: The (18)F-FES tracer could have suitable properties for imaging ER-positive breast tumors. It may provide an important evidence for individualized treatment of patients with breast cancer.