Molecular imaging of steroid hormone receptors in breast cancer for personalized therapy

Author / Creator

Kumar, Manoj, 1984-, author

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Online

Physical

Summary

Breast cancer is the most common cancer in women. The majority of breast cancer overexpress estrogen receptor (ER) and/or progesterone receptor (PR). ER and PR are important prognostic and predicti...

Breast cancer is the most common cancer in women. The majority of breast cancer overexpress estrogen receptor (ER) and/or progesterone receptor (PR). ER and PR are important prognostic and predictive biomarkers. ER is the key driver of breast cancer and is the primary target of endocrine therapy that directly blocks ER function or degrades ER protein, suppressing tumor growth. Despite benefits, endocrine therapy resistance and metastasis remain a significant treatment challenge. Mutations in the ER[alpha] gene (ESR1) have been found in endocrine-therapy resistant breast cancer and are associated with poor patient outcomes. Positron emission tomography (PET) imaging is a highly sensitive non-invasive imaging technology enabling the assessment of ER and PR expression and glucose metabolism in breast cancer. This information could potentially guide treatment decisions based on the presence and functionality of ER as a drug target. In the work presented here, I determined the binding specificity of the PET imaging agent flourine-18 (18F) labeled estradiol (18F-FES) to ER[alpha]. Using preclinical mouse models, I also determined how the most frequently reported activating ESR1 mutations impact 18F-FES binding and in vivo tumor uptake. Finally, I demonstrated that PET imaging of PR expression using 18F-fluorofuranylnorprogesterone (18F-FFNP) is capable of differentiating endocrine therapy effects in breast cancer with activating Y537S ESR1 mutation.

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