Utility of ¹⁸F-fluoroestradiol (¹⁸F-FES) PET/CT imaging as a pharmacodynamic marker in patients with refractory estrogen receptor-positive solid tumors receiving Z-endoxifen therapy

Background: Z-endoxifen is the most potent of the metabolites of tamoxifen, and has the potential to be more effective than tamoxifen because it bypasses potential drug resistance mechanisms attributable to patient variability in the expression of the hepatic microsomal enzyme CYP2D6. ¹⁸F-FES is a positron emission tomography (PET) imaging agent which selectively binds to estrogen receptor alpha (ER-α) and has been used for non-invasive in vivo assessment of ER activity in tumors. This study utilizes ¹⁸F-FES PET imaging as a pharmacodynamic biomarker in patients with ER+ tumors treated with Z-endoxifen. Methods: Fifteen patients were recruited from a parent therapeutic trial of Z-endoxifen and underwent imaging with ¹⁸F-FES PET at baseline. Eight had positive lesions on the baseline scan and underwent follow-up imaging with ¹⁸F-FES 1–5 days post administration of Z-endoxifen. Results: Statistically significant changes (p = 0.0078) in standard uptake value (SUV)-Max were observed between the baseline and follow-up scans as early as 1 day post drug administration. Conclusion: F-FES PET imaging could serve as a pharmacodynamic biomarker for patients treated with ER-directed therapy.