Background/Purpose: Measurement of estrogen receptor (ER) and progesterone receptor (PR) in breast cancer by immunohistochemistry (IHC) is routinely used for prognosis and prediction of benefit from endocrine therapies. Both receptors can be assayed non-invasively by positron emission tomography (PET). ER-PET using 16α-[18F]fluoroestradiol (FES) has been used to predict response to endocrine therapies and evaluate the pharmacodynamics of ER antagonists. Sequential PET imaging with 2-[18F]fluoro-2-deoxyglucose (FDG), before and after 1 week of tamoxifen or 1 day of estradiol, has proven predictive of patient response to endocrine therapies. Here, we investigate in murine models of endocrine-sensitive and resistant mammary cancer whether longitudinal functional PET imaging of PR with [18F]fluoro-furanyl-norprogesterone (FFNP) would provide a predictive measure of response to endocrine therapies that is more rapid and sensitive than ER-PET or sequential FDG-PET.
Methods: FDG, FES and FFNP uptake in murine mammary tumors was quantified serially using microPET imaging before or on days 3 and 4 after ovariectomy. Tumor PR levels were assayed independently by IHC.
Results: The levels of FES and FDG tumor uptake remained unchanged in endocrine-sensitive tumors after ovariectomy compared to those at pre-treatment. By contrast, estrogen deprivation therapy led to a reduction in PR expression (by IHC) and FFNP uptake in endocrine-sensitive tumors, but not in endocrine-resistant tumors, as early as 3 days post-treatment. Unlabeled PR ligand R5020 blocked FFNP tumor uptake, indicating that uptake was due to binding by PR.
Conclusion: Reduction in FFNP tumor uptake, measured conveniently and non-invasively by PET, predicts sensitivity to estrogen deprivation therapy and is more sensitive than FES-PET and FDG-PET. Therefore, longitudinal noninvasive PET imaging using FFNP should be evaluated as a robust and effective approach to predict tumor responsiveness of human breast tumors to endocrine treatments.
(Supported by NIH R01CA025836 and U01CA141541)