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PET/CT using 16α-[ 18 F]-fluoro-17β-estradiol (FES) noninvasively images tissues expressing estrogen receptors (ERs). FES has undergone extensive clinicopathologic validation for ER+ breast cancer and received FDA approval in 2020 for clinical use as an adjunct to biopsy in patients with recurrent or metastatic ER+ breast cancer. Clinical use of FES PET/CT is increasing, but is not widespread in the United States. This AJR Expert Panel Narrative Review explores the present status and future directions of FES PET/CT, including image interpretation, existing and emerging uses, knowledge gaps, and current controversies. Specific controversies discussed include whether both FES PET/CT and FDG PET/CT are warranted in certain scenarios, whether further workup is required after negative FES PET/CT results, whether FES PET/CT findings should inform endocrine therapy selection, and whether immunohistochemistry should remain the standalone reference standard for determining ER status for all breast cancers. Consensus opinions from the panel include agreement with the appropriate clinical uses of FES PET/CT published by a multidisciplinary expert workgroup in 2023; anticipated expanded clinical use of FES PET/CT for staging ER-positive invasive lobular carcinomas and low-grade invasive ductal carcinomas pending ongoing clinical trial results; and the need for further research regarding use of FES PET/CT for ER-expressing nonbreast malignancies.

OBJECTIVE. The purpose of this study was to determine the diagnostic accuracy of 68 Ga-labeled prostate-specific membrane antigen 11 (PSMA-11) PET for disease detection in patients with prostate cancer who have biochemically recurrent disease after radiation therapy or prostatectomy. SUBJECTS AND METHODS. One hundred fifty patients underwent 68 Ga-PSMA-11 PET/CT or PET/MRI, and the images were interpreted by two blinded board-certified radiologists. Each reader evaluated for the presence or absence of PSMA-positive disease within the prostate bed, pelvic lymph nodes, bones, and soft tissues (extrapelvic lymph nodes and visceral structures). The presence or absence of disease was confirmed by histopathologic analysis if available. For patients who did not have pathologic analysis, a composite of imaging and clinical follow-up was used as the reference standard. RESULTS. The median prostate-specific antigen level was 2.1 ng/mL. Forty-three patients had pathologic correlation, and for 29 patients a composite of imaging and follow-up was used to determine the presence or absence of disease. With substantial to almost perfect interreader reliability by region (κ = 0.78-0.87), 68 Ga-PSMA-11 PET had high sensitivity per region (up to 100%) and per patient (up to 89.8%). It also had high positive predictive value per region (up to 100%) and per patient (up to 91.5%). Sensitivity was highest for bone metastases and lowest for soft-tissue metastases. Positive predictive value was highest for bone metastases and lowest for prostate bed recurrence. CONCLUSION. Gallium-68-labeled PSMA-11 PET is sensitive for prostate cancer metastases in patients with biochemically recurrent prostate cancer. It has high positive predictive value and substantial to almost perfect interrater reliability.

Objective: The purpose of this article is to describe the large number of radiotracers being evaluated for prostate-specific membrane antigen (PSMA) PET, which is becoming a central tool in the staging of prostate cancer., Conclusion: PSMA PET is a highly promising modality for the staging of prostate cancer because of its higher detection rate compared with that of conventional imaging. Both PET/CT and PET/MRI offer benefits with PSMA radiotracers, and PSMA PET findings frequently lead to changes in management. It is imperative that subsequent treatment changes be evaluated to show improved outcomes. PSMA PET also has potential applications, including patient selection for PSMA-based radioligand therapy and evaluation of treatment response.