title: Current applications of PET imaging of sex hormone receptors with a fluorinated analogue of estradiol or of testosterone.
abstract: Currently, the most frequent approach in the oncologic applications of positron emission tomography (PET) is detecting the hypermetabolic activity of the cancer tissue. A more specific approach, which may be complementary, is detecting the overexpression of receptors. In this review article, we aim to evaluate the results that are currently available for PET imaging of the sex hormone receptors in clinical oncology. The indication of PET and now PET/CT has been more disputed in breast carcinoma than in many other primary cancers (e.g., lung, head and neck, colorectal, lymphoma). 18F-fluorodeoxyglucose (FDG), the glucose analogue for PET imaging, has a limited sensitivity to detect the primary breast tumors in case of lobular or in situ forms or small sized tumors localised on systematic mammography, and to identify minimal node invasion in the axilla. Using 16α-[¹⁸F]fluoro-17β-estradiol (FES), a fluorinated estradiol analogue, PET is able to detect the over-expression of the oestrogen receptor (ER) in lesions, at a whole-body level. FES and FDG appear complementary for a better diagnostic performance in staging locally advanced breast cancer or restaging recurrent or metastatic breast cancer. Another potential indication is predicting the response to starting or resuming hormone therapy in patients with metastatic breast cancer, in relation with the ER status of all lesions revealed by FES PET. In two retrospective studies, FDG PET was also able to predict the response to hormone therapy, on basis of a metabolic flare, observed either after 7-10 days of treatment or during an estradiol challenge. A prospective comparison of those approaches is warranted. One study reported predicting response to neoadjuvant chemotherapy thanks to a low value of FES SUV(max) or FES/FDG SUV(max) ratio. The presence of ER in uterine tumors, including the benign ones, in ovarian cancers or even in meningiomas, may have therapeutic consequences and FES PET could have a clinical utility in those settings; only initial results are available. The indication of PET and PET/CT has been even more disputed in prostate carcinoma, due to the lack of significant FDG uptake in most cases, at least before the castration-resistant stage. Using FDHT, a fluorinated testosterone analogue, PET is able to detect the over-expression of the androgen receptor (AR) in lesions, at a whole-body level. At least partly due to the rather large number of alternative tracers that are in development or even routinely available in some countries, few FDHT studies have been published until now. From absorbed dose values previously published for FES by the team of University of Washington School of Medicine at Seattle, and for FDHT by the teams of Memorial Sloan-Kettering Cancer Center at New York and of Washington University at St. Louis, we applied the coefficients of ICRP publication 103 and calculated an effective dose per unit of injected activity of 0.023 mSv/MBq for FES and 0.018 mSv/MBq for FDHT. The radiation exposure is of the same order of magnitude as with FDG.
authors.affiliation: Department of Nuclear Medicine, Hôpital Tenon AP‑HP et Université Pierre et Marie Curie, Paris, France - jean-noel.talbot@tnn.aphp.fr.
authors.forename: J N
authors.initials: JN
authors.lastname: Talbot
authors.forename: J
authors.initials: J
authors.lastname: Gligorov
authors.forename: V
authors.initials: V
authors.lastname: Nataf
authors.forename: F
authors.initials: F
authors.lastname: Montravers
authors.forename: V
authors.initials: V
authors.lastname: Huchet
authors.forename: L
authors.initials: L
authors.lastname: Michaud
authors.forename: J
authors.initials: J
authors.lastname: Ohnona
authors.forename: S
authors.initials: S
authors.lastname: Balogova
authors.forename: O
authors.initials: O
authors.lastname: Cussenot
authors.forename: E
authors.initials: E
authors.lastname: Daraï
authors.forename: J P
authors.initials: JP
authors.lastname: Lotz
authors.forename: K
authors.initials: K
authors.lastname: Kerrou
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism*; D004958:Estradiol / Q000493:pharmacokinetics*; D005260:Female; D005462:Fluorine Radioisotopes / Q000493:pharmacokinetics; D006801:Humans; D008297:Male; D057054:Molecular Imaging / Q000379:methods; D049268:Positron-Emission Tomography / Q000379:methods*; D011471:Prostatic Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D011944:Receptors, Androgen / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011987:Receptors, Steroid / Q000378:metabolism*; D013739:Testosterone / Q000493:pharmacokinetics*; D014018:Tissue Distribution
chemical_list: D014408:Biomarkers, Tumor; D005462:Fluorine Radioisotopes; D019275:Radiopharmaceuticals; D011944:Receptors, Androgen; D011960:Receptors, Estrogen; D011987:Receptors, Steroid; D013739:Testosterone; D004958:Estradiol