Preclinical imaging of progesterone receptor signals biomarker usefulness in determining effectiveness of therapy
PET imaging of steroid hormone receptors predict response to endocrine therapy in a preclinical model of breast cancer
Research published in the July issue of The Journal of Nuclear Medicine shows that imaging of progesterone receptor (PR) status may also be able to identify responders and non-responders to endocrine therapy at an early stage. Oestrogen receptor-α(ERα) status is an important factor in determining the most appropriate treatment for breast cancer patients, especially for those who are ERα+ and likely to respond well to hormone-based, or endocrine, therapies.
Prominent professor and research chemist Michael Welch, PhD, who passed away in May, was a contributing author for this research. Throughout his career, Dr Welch specialized in the synthesis of new radiolabeled compounds for medical imaging, with a special emphasis on the growing numbers of applications in PET. Positron emission tomography, or PET, has typically been used to identify the target for endocrine therapy in breast cancer by demonstrating that ER is present in tumours using F-18-fluoroestradiol (FES)-PET, or by monitoring for hormone-induced changes in tumour metabolism—‘metabolic flare’— with F-18-fluorodeoxyglucose (FDG)-PET once therapy has begun. What is novel about this study is that the investigators chose to image progesterone receptor levels to see how the oestrogen signalling pathway is functioning in response to endocrine therapy.
Imaging of progesterone receptor levels to evaluate how the oestrogen signalling pathway functions in response to endocrine therapy
In this study, mice with mammary cell lines (SSM1, SSM2 and SSM3) derived from STAT1-deficient mammary tumours—which are ERα+/PR+ and similar to the majority of human breast cancers—were imaged. Small-animal PET/computed tomography (CT) was performed using F-18-FES to image oestrogen receptor status, F-18-fluoro furanyl norprogesterone (F-18-FFNP) for progesterone receptor status, and FDG for glucose uptake.
Initial imaging of the cell lines showed that SSM3 tumours displayed the greatest F-18-FES and F-18-FFNP uptake, and therefore, the SSM3 cell line was used to test the response to estradiol, an ER agonist, and fulvestrant, a pure ER antagonist. Upon treatment with estradiol, it was determined that PR expression is oestrogen-inducible and indicative of ERα signalling in the SSM3 tumours. Mice treated with fulvestrant showed early decreases in F-18-FFNP uptake after initiation of therapy, prior to measurable growth inhibition. SSM2 tumours, which were not growth-inhibited by fulvestrant despite also being ERα+/PR+, showed no change in F-18-FFNP uptake after initiation of therapy. These data support the potential use of PR imaging with F-18-FFNP PET of patients with ERα+ breast cancer at baseline and shortly after initiation of endocrine therapy to distinguish between responders and non-responders, and thus help facilitate the selection of therapies most appropriate for individual patients.
An important goal of molecular imaging in cancer research is to noninvasively predict early responses to therapies in order to guide further management. According to Dr Amy Fowler, lead author of the study, this work using a preclinical model of breast cancer helps support the notion that molecular imaging can achieve this goal by testing whether the target utilized for a specific therapy is not only present but also functional.
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