[18F]-fluoroestradiol quantitative PET imaging to differentiate ER plus and ERα-knockdown breast tumors in mice

Introduction: The purpose of this study was to develop a noninvasive model in tumor-bearing mice to investigate the use of 16 alpha-[F-18] fluoro-17 beta-estradiol (FES) positron emission tomography (PET) imaging as a tool to discriminate between tumors having different estrogen receptor (ER) alpha status. Methods: MC7-L1 and MC4-L2 murine mammary adenocarcinoma cell lines (ER+) received a small hairpin RNA targeting the ER alpha gene by lentiviral infection. In vitro assessment of ER alpha levels of the new cell lines (MC7-L1 and MC4-L2 ER alpha-knockdown; ER alpha KD), compared to the parental cell lines, was performed by immunoblouing (-75% ER alpha protein) and binding assays (-50% estrogen binding). These cell lines were implanted subcutaneously in Balb/c mice and allowed to grow up to a volume of at least 20 mm(3). FES and [F-18] fluorodeoxyglucose (FDG) PET images were acquired to measure FES and FDG uptake in the various tumors. Results: FES uptake as assessed by PET imaging was 1.06 +/- 0.21 percent injected dose per gram of tissue (%ID/g) for MC7-L I minors and 0.47 +/- 0.08 %ID/g for MC7-L1 ER alpha KD tumors. MC4-L2 tumors had a FES uptake of 1.03 +/- 0.30 %ID/g, whereas its ER alpha KD equivalent was 0.51 +/- 0.19 %ID/g. Each ER alpha KD tumor had a significantly lower %ID/g value, by similar to 50%, than its ER+ counterpart. Biodistribution studies confirmed these findings and gave %ID/g values that were not significantly different from PET imaging data. FDG PET showed no significant uptake difference between the ER+ and ER alpha KD tumors, indicating that the metabolic phenotype of the ER alpha KD cell lines was not altered. Conclusion: FES PET imaging was able to reliably differentiate between tumors having differences in their ER alpha expression in vivo, in a mouse model. Quantitative data obtained by FES PET were in concordance with biodistribution studies and in vitro assays. It is concluded that FES PET imaging can likely be used to monitor subtle ER status changes during the course of hormone therapy. (C) 2012 Elsevier Inc. All rights reserved.