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

Abstract

To demonstrate how estrogen receptor alpha (ERα) positive breast cancer xenografts may be visualized in BALB/c nude mice using 16α-[18F]-fluoro-17β-estradiol (¹⁸F-FES) positron emission tomography (PET), ovariectomized BALB/c nude mice were injected with ERα-positive breast cancer cells (MCF-7, 3 × 10⁶ cells; shoulder [n = 10] or 4^th inguinal mammary fat pad [n = 10]) or ERα-negative breast cancer cells (MDA-MB-231, 1 × 10⁶ cells; mammary fat pad [n = 5]). Mice harboring MCF-7 cells received subcutaneous injections of 20 µg of 17β-estradiol (20 µg/20 µL; 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, 17β-estradiol injections were halted 2 days prior to mice receiving ¹⁸F-FES for PET imaging to avoid competitive binding with ERα. 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 ERα-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 ERα expression in ERα-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.