Using 16α-[18F]-Fluoro-17β-Estradiol PET to Visualize Estrogen Receptor α Expression in Human Breast Cancer Xenografts in Female Ovariectomized Mice

To demonstrate how estrogen receptor alpha (ER alpha) positive breast cancer xenografts may be visualized in BALB/c nude mice using 16 alpha-[18F]-fluoro-17 beta-estradiol (18F- FES) positron emission tomography (PET), ovariectomized BALB/c nude mice were injected with ER alpha-positive breast cancer cells (MCF-7, 3 x 106 cells; shoulder [n = 10] or 4th inguinal mammary fat pad [n = 10]) or ER alpha-negative breast cancer cells (MDAMB-231, 1 x 106 cells; mammary fat pad [n = 5]). Mice harboring MCF-7 cells received subcutaneous injections of20 mu g of 17 beta-estradiol (20 mu g/20 mu L; corn oil:ethanol, 9:1) in the nape of their necks 2 days prior to cell injection, followed by daily injections five times per week for 5 weeks. Tumor volumes were measured according to the formula: (L*W2)/2 (L; length, W; width). Once tumor volumes reached approximately 100 mm3, 17 beta-estradiol injections were halted 2 days priorto mice receiving 18F-FES for PET imaging to avoid competitive binding with ER alpha. Upon 18F-FES administration via the lateral tail vein, PET/MRI was performed for 15 min at 1 h to 1.5 h post- injection. 18F-FES uptake was not observed in ER alpha-negative, MDA-MB-231 tumor- bearing mice. 18F-FES uptake was most pronounced in mice harboring MCF-7 tumors in the shoulder. In MCF-7 tumors grown in the inguinal mammary fat pad, 18F-FES uptake was less visible, as the intestinal excretion pattern of 18F-FES obscured the radioactivity detectable in these tumors. To use 18F-FES PET as a tool to visualize ER alpha expression in ER alpha-positive breast xenografts, we demonstrate that the visibility of 18F-FES uptake is clear in tumors located away from the abdominal region of mice, such as in the shoulder.