Several imaging techniques, including ultrasound, computed tomography and magnetic resonance imaging (MRI), have been used for the detection of DIE, for mapping and staging endometriosis. Currently, the modalities most commonly used are transvaginal ultrasound (TVS) and magnetic resonance imaging MRI. TVS is generally considered a first-line technique.TVS, in highly experienced hands, meets the criteria for mapping DIE to the uterosacral ligaments, rectovaginal septum, vaginal wall, pouch of Douglas and rectosigmoid; however it is limited by its operator dependance and by the small field of view (FOV). MRI is commonly used for mapping lesions within the Douglas pouch and rectovaginal septum and rectosigmoid. MRI has shown acceptable diagnostic values, with pooled sensitivity and specificity for pelvic endometriosis of 94% and 77%, respectively. For rectosigmoid endometriosis, MRI's pooled sensitivity and specificity were 92% and 96%, respectively. However, MRI has limitations, specially in the evaluation of chronic fibrotic endometriosis and for assessing the peritoneum and extension beyond the pelvis as well as DIEs. There is a growing body of literature examining the role of PET/MRI in pelvic and abdominal malignancies and its potential superiority to MRI alone. However, there are no studies that used PET/MRI to investigate endometriosis.

This study aims to use \[68Ga\]CBP8- or \[18F\]FAPI PET/MRI to diagnose and quantify endometriosis. The novel radiopharmaceutical collagen-binding probe 8 labeled with Gallium-68 selectively binds to collagen type I, the predominant extracellular protein in fibrosis. \[68Ga\]CBP8 has already been investigated in patients affected by pulmonary fibrosis with success. Fibroblast activation protein (FAP) is a type II transmembrane serine protease that is overexpressed in CAFs and, to a lesser extent, in benign processes. It is associated with extracellular matrix remodeling, for example, chronic inflammation, degenerative bone and spine disease, arthritis, and cardiac remodelling after myocardial infarction. Quinolone-based FAP inhibitors (FAPIs) constitute a class of molecules with high affinity to FAP deployed to assess many types of solid tumors and some benign pathologies. 68Ga-FAPIs and, to a lesser extent, 18F-FAPI are being extensively studied in oncologic and non-oncologic positron emission tomography/computed tomography (PET/CT) and, to a lesser extent, PET/MRI, both in Europe and Asia.

In this single-arm, single-center, open label prospective study, the authors will recruit 60 patients with clinical diagnosis of endometriosis who candidate for laparoscopic surgery. Patients will be referred to FAPI- or CBP8-PET/MRI by their primary treating gynecologist physicians. Laparoscopy will serve as primary standard of reference; clinical and imaging follow up, as well as prior diagnostic imaging studies (CT, MRI, US), will serve as secondary standard of reference. In the case patients will not undergo laparoscopy, then clinical and imaging follow up, as well as prior diagnostic imaging studies (CT, MRI, US), will serve as primary standard of reference.

Board-certified radiologists will evaluate \[18F\]-FAPI-74 or \[68Ga\]CBP8-PET/MR images and standalone MR images in a blinded fashion on separate occasions. Assessment of of endometriosis will be performed according to consolidated published criteria for MRI. For endometriosis staging, the readers will follow rASRM criteria. Then, the authors will compare the sensitivity, specificity, and accuracy of regional/whole-body staging using FAPIor CBP-PET/MRI versus regional/wholebody MRI, with the standard reference set as pathology results, when available, or clinical and imaging follow-up otherwise. Hypothesis testing will be performed using McNemar's test for matched pairs testing.