Improved Estrogen Receptor Assessment by PET Using the Novel Radiotracer ¹⁸F-4FMFES in Estrogen Receptor–Positive Breast Cancer Patients: An Ongoing Phase II Clinical Trial

Abstract

After encouraging preclinical and human dosimetry results for the novel estrogen receptor (ER) PET radiotracer 4-fluoro-11β-methoxy-16α-¹⁸F-fluoroestradiol (¹⁸F-4FMFES), a phase II clinical trial was initiated to compare the PET imaging diagnostic potential of ¹⁸F-4FMFES with that of 16α-¹⁸F-fluoroestradiol (¹⁸F-FES) in ER-positive (ER+) breast cancer patients. <b>Methods:</b> Patients diagnosed with ER+ breast cancer (<i>n</i> = 31) were recruited for this study, including 6 who underwent mastectomy or axillary node dissection. For each patient, ¹⁸F-FES and ¹⁸F-4FMFES PET/CT scans were done sequentially (within a week) and in random order. One hour after injection of either radiotracer, a head-to-thigh static scan with a 2-min acquisition per bed position was obtained. Blood samples were taken at different times after injection to assess each tracer metabolism by reverse-phase thin-layer chromatography. The SUV_mean of nonspecific tissues and the SUV_max of the tumor were evaluated for each detected lesion, and tumor-to-nonspecific organ ratios were calculated. <b>Results:</b> Blood metabolite analysis 60 min after injection of the tracer showed a 2.5-fold increase in metabolic stability of ¹⁸F-4FMFES over ¹⁸F-FES. Although for most foci ¹⁸F-4FMFES PET had an SUV_max similar to that of ¹⁸F-FES PET, tumor contrast improved substantially in all cases. Lower uptake was consistently observed in nonspecific tissues for ¹⁸F-4FMFES, notably a 4-fold decrease in blood-pool activity as compared with ¹⁸F-FES. Consequently, image quality was considerably improved using ¹⁸F-4FMFES, with lower overall background activity. As a result, ¹⁸F-4FMFES successfully identified 9 more lesions than ¹⁸F-FES. <b>Conclusion:</b> This phase II study with ER+ breast cancer patients showed that ¹⁸F-4FMFES PET achieves a lower nonspecific signal and better tumor contrast than ¹⁸F-FES PET, resulting in improved diagnostic confidence and lower false-negative diagnoses.