Positron emission tomography (PET) imaging with 18F-fluorofuranylnorprogesterone (18F-FFNP) may allow early measurement of efficacy of breast cancer therapy.
Physicians may soon have a new way to measure the efficacy or failure of hormone therapy for breast cancer patients, according to new research published in the February issue of The Journal of Nuclear Medicine. Researchers report that positron emission tomography (PET) imaging with 18F-fluorofuranylnorprogesterone (18F-FFNP) has been found to successfully measure changes in progesterone receptor (PR) levels resulting from a short-course estrogen treatment, also known as an estradiol challenge.
By participating in an estradiol challenge, physicians can determine the likelihood of potential benefit of hormonal therapies targeting ER for individual patients. Many hormone therapies interfere with the ability of estrogen to regulate the expression of PR protein, which is more pronounced in the presence of estrogen. As such, several PET tracers have been developed to monitor and analyze changes in the PR level during therapy. "Typically, anatomic size and proliferation biomarkers are analyzed to determine endocrine sensitivity," said Amy M. Fowler, MD, PhD, assistant professor, Section of Breast Imaging, Department of Radiology, University of Wisconsin-Madison. "However, non-invasive detection of changes in PR expression with 18F-FFNP during an estradiol challenge may be an earlier indicator of the effectiveness of a specific hormone therapy."
In T47D cells treated with estrogen, an increase in 18F-FFNP uptake was measured at 48 hours after treatment; in mice with T47D tumor xenografts, increased uptake was seen at 48 and 72 hours after treatment. This increase in 18F-FFNP uptake also correlated with an increase in PR protein expression and proliferation. Results showed that there was no significant preferential 18F-FFNP binding or uptake by PR-A versus PR-B in PR isoform cell lines or tumor xenografts. "This is an important finding given the variability of PR isoform expression observed in breast cancer patients," stated Fowler.
She continued, "Validation of PR imaging as a biomarker of endocrine sensitivity in patients before and after estradiol challenge could provide new opportunities in the field of molecular imaging and nuclear medicine for breast cancer imaging. Improved methods for testing endocrine sensitivity in patients could better inform decisions for optimal individualized ER-positive breast cancer therapy, potentially reducing morbidity and mortality."