Application of 18F-FAPI PET/CT in Deep Infiltrating Endometriosis

A 40′s perimenopausal woman with a history of dysmenorrhea presented with anal tenesmus and increased bowel frequency during menstruation over the past 2 years. Two months prior to admission, a colonoscopy performed in the gastroenterology department revealed a raised lesion in the rectum, with postoperative histopathology confirming endometriotic involvement.

Haili Li: conceptualization, writing – original draft. Tongxin Chen: conceptualization, data curation, investigation, resources, writing – original draft. Ruyu Cai: conceptualization, formal analysis, resources, writing – original draft. Yifan Huang: data curation, formal analysis, supervision, validation. Xiangcheng Wang: methodology, validation, writing – review and editing. Pingyue Yu: investigation, methodology, supervision, visualization. Minge S. Li: project administration, writing – review and editing.

This study was supported by the Sanming Project of Medicine in Shenzhen (NO. SZSM202311011).

The patient underwent surgical resection, with postoperative histopathology confirming all imaging‐suspected lesions as endometriotic foci (Figure  2 ). Gross specimen photograph of the deep infiltrating endometriosis (DIE) lesion in the rectouterine pouch (pouch of Douglas) from this patient.

The most common subtypes of pelvic endometriosis include superficial peritoneal lesions, DIE, and ovarian endometriotic cysts. Primary symptoms encompass dysmenorrhea, dyspareunia, infertility, urinary urgency during menstruation, and anal tenesmus. Although definitive diagnosis of endometriosis is confirmed histologically, preoperative imaging remains critical in clinical practice; however, visualization can be challenging due to the heterogeneous nature of lesions and their highly variable imaging appearances [ 3 ]. TVUS and MRI are currently the most widely used imaging modalities with the highest specificity for endometriosis. However, their sensitivity remains limited and highly operator‐dependent. In a systematic review, Guerriero et al. [ 4 ] reported that for rectosigmoid DIE, both MRI and TVUS demonstrated sensitivities of 85%, with specificities of 95% and 96%, respectively. Conversely, for uterosacral ligament DIE, the sensitivities dropped to 70% for MRI and 67% for TVUS. In the present case, while TVUS indicated an anterior rectal lesion, it failed to delineate its boundaries with adjacent tissues, whereas MRI demonstrated excellent performance, revealing lesions that closely matched intraoperative findings. Recent advances in imaging technology have highlighted the potential of PET as an attractive diagnostic tool, leveraging novel PET tracers combined with superior soft tissue contrast and detailed abdominopelvic anatomical resolution [ 5 ]. A 2016 study found that 18F‐FES PET/CT (18‐Ffluoro‐17β‐estradiol positron emission tomography/computedtomography)outperformed MRI in diagnostic accuracy, achieving a true positive rate of 100% (9/9 suspected lesions confirmed by histopathology) compared to MRI's false‐positive rate of 66.6% [ 6 ]. However, the efficacy demonstrated by different PET probes varies significantly. For instance, a study by Balogova et al. [ 7 ] found that 18F‐FDG PET/CT showed a positive rate of 72% in 18 patients, with 9 patients exhibiting 13 non‐endometriosis‐related lesions showing positivity on imaging, where SUV max ranged between 2.7 and 23. These results were deemed unsatisfactory. Consequently, a novel PET probe has emerged: 18F‐Fibroblast Activation Protein Inhibitor (18F‐FAPI), a PET tracer with high selectivity for fibroblast activation protein. Yangmeihui Song et al. have completed a clinical trial and suggested that FAPI PET has demonstrated significant potential in preclinical experiments and preliminary clinical trials for non‐invasive visualization and dynamic monitoring of hepatic fibrosis, particularly outperforming other common clinical indicators in early stages [ 8 ]. As varying degrees of fibrosis have been confirmed in endometriosis lesions, 18F‐FAPI may serve as an effective PET radiotracers for endometriosis detection. Currently, only three cases of 18F‐FAPI application in endometriosis diagnosis have been reported; 18 F‐FAPI PET/CT accurately diagnosed DIE lesions in all cases [ 9 , 10 , 11 ]. The imaging findings of TVUS and MRI in this case were consistent, both suggesting suspected DIE in the anterior rectal wall. Additionally, MRI indicated potential lesions in the bilateral uterosacral ligaments, which were later confirmed by postoperative pathology. However, 18F‐FDG PET/CT showed no increased uptake in these corresponding lesions. Subsequent 18F‐FAPI PET/CT only detected lesions in the rectouterine pouch but failed to visualize the bilateral uterosacral ligament lesions. This discrepancy might be attributed to CT's inherent limitations in resolving inter‐tissue relationships compared to MRI, which demonstrates superior soft tissue differentiation capabilities.

The written informed consent was obtained from the patient.

She was subsequently referred to the gynecology department for hospitalization. Pre‐admission transvaginal ultrasonography (TVUS) and pelvic magnetic resonance imaging (MRI) both suggested possible DIE in the anterior rectal wall. To further guide treatment planning, pelvic 18F‐FDG PET/CT (18F‐Fludeoxyglucose positron emission tomography/computedtomography)was performed post‐admission; however, the results were suboptimal, showing no definitive 18F‐FDG‐avid foci in the rectovaginal septum, which was inconsistent with the preoperative MRI findings (Figure  1B,D ). Consequently, supplementary 18F‐FAPI PET/CT (Fibroblast Activation Protein Inhibitor PET/CT) was conducted, demonstrating ill‐defined soft tissue density between the uterus and rectum, adjacent to mild thickening of the anterior rectal wall. The lesion exhibited intense 18F‐FAPI uptake (maximum diameter: 2.0 cm, SUV max  = 7.5), corresponding precisely to the MRI‐identified location, thereby validating the MRI results (Figure  1A,C ). (A) (18F‐FAPI PET/CT) demonstrates a high uptake (SUV max  = 7.5) in the rectouterine pouch (pouch of Douglas), whereas (B) (18F‐FDG PET/CT) exhibits diffuse uterine uptake with no significant tracer accumulation in the same region. (C, D) display coronal and sagittal views of 18F‐FAPI and 18F‐FDG PET/CT, respectively. Consistent with the axial images, only (C) (18F‐FAPI PET/CT) reveals a well‐defined high uptake lesion (diameter: ~2.0 cm, SUV max  = 7.5) in the rectouterine pouch, while (D) (18F‐FDG PET/CT) shows nonspecific background activity.

Studies over the past two decades have demonstrated that endometriosis is an estrogen‐dependent chronic inflammatory process affecting pelvic tissues. The most severe phenotype is DIE, which is defined as subperitoneal lesions that penetrate tissue deeper than 5 mm under the peritoneal surface (such as the uterosacral ligaments) or as lesions that infiltrate the muscularis propria of the organs that surround the uterus. For example, the bladder, intestine with or without occlusion, and ureter with or without ureterohydronephrosis [ 1 , 2 ]. The predominant symptoms include dysmenorrhea, dyspareunia, and infertility. Lesions invading the bladder may cause urinary urgency and frequency, while rectal involvement may lead to anal tenesmus and constipation, severely impacting patients' quality of life. Current clinical diagnostic strategies integrate medical history, physical examination findings, serum markers, and imaging modalities [ 2 ]. However, the gold standard remains histopathological confirmation following surgical intervention.

The authors declare no conflicts of interest.

Certainly, given that 18 F‐FAPI PET/CT also exhibits high uptake in most malignancies—notably ovarian cancer—its use for DIE lesion visualization carries a risk of potential false positives. This necessitates validation through extensive clinical trial data in future studies.