PET Imaging Agents (FES, FFNP, and FDHT) for Estrogen, Androgen, and Progesterone Receptors to Improve Management of Breast and Prostate Cancers by Functional Imaging

Abstract

Many breast and prostate cancers are driven by the action of steroid hormones on their cognate receptors in primary tumors and in metastases, and endocrine therapies that inhibit hormone production or block the action of these receptors provide clinical benefit to many but not all of these cancer patients. Because it is difficult to predict which individuals will be helped by endocrine therapies and which will not, positron emission tomography (PET) imaging of estrogen receptor (ER) and progesterone receptor (PgR) in breast cancer, and androgen receptor (AR) in prostate cancer can provide useful, often functional, information on the likelihood of endocrine therapy response in individual patients. This review covers our development of three PET imaging agents, 16α-[18F]fluoroestradiol (FES) for ER, 21-[18F]fluoro-furanyl-nor-progesterone (FFNP) for PgR, and 16β-[18F]fluoro-5α-dihydrotestosterone (FDHT) for AR, and the evolution of their clinical use. For these agents, the pathway from concept through development tracks with an emerging understanding of critical performance criteria that is needed for successful PET imaging of these low-abundance receptor targets. Progress in the ongoing evaluation of what they can add to the clinical management of breast and prostate cancers reflects our increased understanding of these diseases and of optimal strategies for predicting the success of clinical endocrine therapies.

The influence of 18F-fluorodeoxyglucose positron emission tomography/computed tomography on the N- and M-staging and subsequent clinical management of intrahepatic cholangiocarcinoma

“…As molecular targeted therapy and immunotherapy have becoming increasingly important in ICC (33)(34)(35)(36), such scenario may come to a reality in the near future. Apart from 18 F-FDG, more novel imaging agents such as 11 C-fluorocholine, 18 F-fluoroestradiol, and 18 F-fluorothymidine, have been tested and applied in cancers (37,38). Targeting tumor-specific biomarkers and metabolism with optimal imaging agent are promising in PET/CT, such as the 68 Ga-prostate specific membrane antigen (PSMA) PET in detecting metastasis of prostate cancer (39).…”

Clinical perspectives for the use of total body PET/CT

“…In the same way, several new agents targeting hormonereceptors could improve management of hormone-dependent cancers [32]. The most studied was the 18FES for breast cancers presenting estrogen receptors (ER) [33].…”

ZR-75-1 breast cancer models to study the utility of 18F-FES by PET imaging

“…18 F-FES uptake in ER-negative organs, such as the lungs, muscle and brain, peaked at 15 minutes post injection, were lower than that in tumors. In addition, 18 F-FES uptake in bone was low which indicates minimal defluorination for 18 F-FES in vivo (27). The T/M ratio were increased over time, imaging 30 minutes after injection may produce good visualization of ER-positive tumors (28).…”