Study: PET confirms efficacy of estrogen-blocking drugs
18F-fluoroestradiol (FES) PET can assess the in vivo pharmacodynamics of estrogen receptor (ER)-targeted agents and may give insight into the activity of established therapeutic agents, according to a study in the August issue of Clinical Cancer Research.

Hannah M. Linden, MD, of the department of medicine at the University of Washington School of Medicine in Seattle, and colleagues sought to determine, by molecular imaging, how in vivo pharmacodynamics of estrogen-ER binding differ between types of standard endocrine therapy.

The ER has been a highly successful target for breast cancer treatment. ER-directed treatments include lowering ligand concentration by using aromatase inhibitors and blocking the receptor with agents like tamoxifen or fulvestrant.

The researchers measured regional estrogen-ER binding by using PET with FES prior to and during treatment with aromatase inhibitors, tamoxifen (Nolvadex, Istubal, Valodex; AstraZeneca) or fulvestrant (Faslodex; AstraZeneca) in a series of 30 metastatic breast cancer patients. FES PET measured in vivo estrogen binding at all tumor sites in heavily pretreated women with metastatic bone soft tissue-dominant breast cancer. In patients with uterus changes (16 patients), uterine FES uptake was also measured.

As the authors “expected,” tumor FES uptake declined more markedly on ER blockers (tamoxifen and fulvestrant, average 54 percent decline) compared with a less than 15 percent average decline on estrogen-depleting aromatase inhibitors.

The rate of complete tumor blockade [FES standardized uptake value (SUV)] following tamoxifen (five out of five patients) was greater than the blockade rate following fulvestrant (four out of 11), Linden and colleagues wrote. Percent FES SUV change in the uterus showed a strong association with tumoral change.

“Imaging revealed significant differences between agents, including differences in the efficacy of blockade by different ER antagonists in current clinical use,” the authors wrote.

“What we're suggesting in the paper—that we couldn't fully test for before—is if estrogen is incompletely blocked you're not getting a good outcome for the patient,” Linden said in a statement.

“Our findings support the ability of FES PET to visualize the in vivo activity of endocrine therapy,” the authors concluded. “This technology could be used early in drug development to measure effectiveness at the intended therapeutic targets, and to help refine selection and dosing for agents to move forward in drug development.”

Additionally, pharmacodynamic imaging could provide clinicians with a promising tool for therapeutic selection and for predicting and evaluating response to estrogen-receptor-targeted therapy, Linden said.