Fluoroestradiol PET-MRI imaging for detection of endometriosis lesions and symptom correlation.

Am J Nucl Med Mol Imaging 2024;14(3):182-188 www.ajnmmi.us /ISSN:2160-8407/ajnmmi0154100 Original Article Fluoroestradiol PET-MRI imaging for detection of endometriosis lesions and symptom correlation Jorge D Oldan1, Yueh Z Lee1, Kristen OIinger1, Thad S Benefield1, Erin T Carey2, Noor D Abu-Alnadi2, Steven L Young2 Department of Radiology, University of North Carolina School of Medicine, 2000 Old Clinic, Campus Box 7510, Chapel Hill, NC 275997510, United States of America; 2Department of Obstetrics and Gynecology, University of North Carolina School of Medicine, 4010 Old Clinic Building, Campus Box 7570, United States of America 1 Received October 25, 2023; Accepted February 23, 2024; Epub June 15, 2024; Published June 30, 2024 Abstract: Endometriosis is a common cause of infertility, pelvic pain, and dysmenorrhea and there are prior case reports of lesion detection using an 18F-fluoroestradiol (FES) tracer with positron emission tomography (PET). We aimed to further investigate the use of the FES tracer in the context of PET-magnetic resonance (PET-MR) imaging. We administered FES to 6 patients and then imaged them using a Siemens mMR PET-MR scanner. Each patient was taken to surgery within 30 days after imaging, and surgical visualization served as the gold-standard for diagnosis. PET did not prove to be as sensitive as MR (50% per-patient sensitivity versus 67% per-patient and 35% versus 48% per-lesion), and did not show any additional sites over and above MR. When MR was used to localize lesions on PET after imaging, there was insufficient evidence of an association between total tracer uptake and reported pain intensity (P=0.25). FES PET-MR offers no additional value to MR for endometriosis. Keywords: Positron emission tomography, magnetic resonance imaging, imaging, endometriosis, pelvic pain Introduction Endometriosis is a chronic inflammatory disorder that affects approximately 1 in 10 reproductive-aged women [1, 2], and is a significant cause of both pelvic pain and infertility [3]. Endometriosis is diagnosed by the expression of estrogen-sensitive endometrial-like glands and stroma outside the uterus. Three clinical phenotypes of endometriosis have been described: superficial endometriotic implants on the peritoneum, endometriomas, and deeply infiltrating endometriosis (a nodule extending ≥5 mm beneath the peritoneum). Despite the disease prevalence, definitive diagnosis of endometriosis is often significantly delayed, with time between onset symptoms and diagnosis exceeding 5 years globally, and upper estimates 7-10 years [4]. This diagnostic delay in endometriosis is multifaceted. Endometriosis symptoms frequently overlap with other pain conditions (i.e. primary dysmenorrhea, irritable bowel syndrome, pelvic floor dysfunction) or simply present as infertility without significant pain. Imaging is often used in the investigation of chronic pelvic pain, however imaging sensitivity for endometriosis varies depending on the lesion phenotype and size, with early stage disease often undetectable by non-surgical approaches. There are also no reliable diagnostic biomarkers in blood or urine available. At present, visualization and/or histological examination of surgically-directed biopsies are the only usable diagnostic modality for the detection of stage 1 or stage 2 disease. As surgical intervention is associat- ed with risk, empiric treatments of suspected disease are frequently utilized in clinical practice [5]. Even more advanced endometriosis and deeply infiltrating lesions can be difficult to diagnose preoperatively. While pelvic ultrasonography has the highest sensitivity and specificity in identifying ovarian endometriomas, it is not nearly as sensitive at the detection of deeply infiltrative or peritoneal lesions [2, 4]. Magnetic resonance imaging (MRI) also has high sensitivity and specificity for identifying ovarian endometriomas, but detection of superficial peritoneal endometriosis by MRI alone is often unachievable and adequate detection of deep infiltrating endometriosis (DIE) by US and/or MRI often requires specific training and approach. Cross-sectional imaging techniques, including computed tomography and magnetic resonance imaging (MRI) have limited utility in identifying endometriomas, though MRI has increased sensitivity and specificity in deeply infiltrative lesions and colonic disease [6]. Diagnostic delay compounded by the inability to identify and monitor early-stage lesions limits our ability to understand disease pathogenesis and progression as well as to monitor disease response to current therapeutic interventions and greatly limits the development of novel therapeutics. Positron emission tomography (PET) offers the potential for a molecular-based imaging for highly specific diagnosis and monitoring of endometriosis. Endometriotic lesions, including endometriomas, express the estrogen receptors ERa and ERb, which bind specifically to estrohttps://doi.org/10.62347/JOQM7920 FES PET-MR for endometriosis gen and estrogen analogs such as FES [7, 8]. This has already allowed the tracer to find a clinical role in the diagnosis of breast cancer, in finding previously more occult tumors like invasive lobular carcinoma [9], selecting patients for hormonal therapies, and assessing status in difficult-to-biopsy lesions [10]. The objective of our study was to evaluate the preoperative diagnostic performance of 18-fluoroestradiol (FES) for detecting endometriosis, compared to surgical staging and patient symptom severity. Materials and methods We conducted a single-site, prospective pilot study. The primary end point of the study was the feasibility of PET/ MRI imaging with FES to identify endometriosis lesions and compared to diagnosis at surgery, the current gold standard. Recruitment and surveys Inclusion criteria were women aged 18-50 with suspected superficial or peritoneal endometriosis or extragenital DIE with the need for laparoscopic confirmation/resection as determined by the minimally invasive gynecologic surgery team. They also had to have a willingness to undergo experimental imaging. Exclusion criteria included the use of hormone treatments (combined oral contraceptives, progestins, gonadotropin releasing hormone analogs) for at least two cycles, or pregnancy/breastfeeding. Demographics were abstracted from the electronic medical record and patients completed the Endometriosis Health Profile-30 (EHP-30) [11]. A pain numeric rating scale (NRS) was collected and information about the last menstrual period were also obtained. Patients underwent FES PET/ MRI (positron emission tomography/magnetic resonance imaging) within 30 days of the scheduled surgery and the surgical team was blinded to the imaging findings. Immediately postoperatively the surgeon completed the revised American Society for Reproductive Medicine (ASRM) classification of endometriosis form [12, 13]. Postoperatively, the imaging findings were compared to surgical (...truncated)