A molecular imaging technique using PET technology may improve how the efficacy or failure of hormone therapy is measured for breast cancer patients, according to research published online in the February issue of The Journal of Nuclear Medicine.
Researchers from the University of Wisconsin School of Medicine and Public Health in Madison, Wisconsin, found that positron emission tomography (PET) imaging with 18F-fluorofuranylnorprogesterone (18F-FFNP) can successfully measure changes in progesterone receptor (PR) levels which results from a short-course estrogen treatment, also known as an estradiol challenge.
“Typically, anatomic size and proliferation biomarkers are analyzed to determine endocrine sensitivity,” lead author Amy M. Fowler, MD, PhD, as assistant professor in the Breast Imaging Section of the department of radiology at the University of Wisconsin-Madison, said in a prepared statement. “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.”
For the study, Fowler and colleagues treated T47D human breast cancer cells (cells with estrogen and progesterone receptors, but without human epidermal growth factor receptor-2) and mice bearing T47D tumor xenografts with estrogen to increase PR levels.
PET images of the cells and mice were then imaged were taken with 18F-FFNP to measure cell uptake and tissue biodistribution. To investigate the separate role of PR-A and PR-B isoforms on overall 18F-FFNP binding, triple-negative MDA-MB-231 breast cancer cells were engineered to express either PR-A or PR-B, according to the researchers. Additionally, in vitro 18F-FFNP binding was measured by saturation and competitive binding assays, while in vivo uptake was measured with PET imaging.
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, the researchers wrote. There was overall no significant preferential 18F-FFNP binding or uptake by PR-A versus PR-B in PR isoform cell lines or tumor xenografts.
“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,” Fowler said in a prepared statement. “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.”