PET/MRI for Evaluation of Endometriosis

N/AEnrolling By InvitationNCT06377553

Massachusetts General Hospital60 enrolled

Overview

This study aims to determine if PET/MRI can detect endometriosis and potentially improve upon currently available non-invasive diagnostic capabilities. Specifically, the authors will investigate the ability of PET/MRI to detect and quantify endometriosis, as well as differentiate among subcategories such as inflammatory peritoneal lesions, fibrotic deep infiltrating endometriosis lesions (DIE), and ovarian endometriomas. The authors will compare \[68Ga\]CBP8 or \[18F\]-FAPI-74 PET/MRI imaging versus the current gold standard diagnostic methods, including laparoscopic surgery, clinical follow-up, and follow-up imaging.

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.

Interventions

Radiotracer InjectionDRUG

An intravenous catheter will be placed in an arm or hand vein for injection of \[68Ga\]CBP8; 6-10 mCi of \[68Ga\]CBP8 or 5-9 mCi of FAPI will be injected into the Biograph mMR system. The injected dose and the time of injection will be recorded; The catheter will be flushed with 0.9% saline solution; The subjects will then be positioned on the scanner table; support devices under the back or legs will be used to enable the patient to maintain his/her position throughout the scan comfortably.

ImagingDIAGNOSTIC_TEST

MRI and PET scanner to be used: 3.0 T Laboratory (Bay 7) Siemens Biograph mMR. Magnetic resonance images of the pelvis and abdomen will be acquired using the Martinos Center's combined 3 Tesla PET/MRI scanner. The image quality on these 3 Tesla devices will be very high, equivalent to or better than any other standard clinical MRI system. PET images of the target body site will be acquired when necessary, the data acquisition will be started shortly before radiotracer injection; Coincidence event data will be acquired and stored in list mode or compressed (i.e., sinogram space) format. Subjects will be asked to lie still for the duration of the study. The entire imaging session will last up to 120 minutes

Rectal Ultrasound Gel InjectionOTHER

About 50ml of ultrasound gel will be placed into the vagina using the blunt end of the ultrasound gel tube or a Foley catheter or a syringe with a blunt Christmas tree end. No ultrasound probe will be inserted into the vagina, no external ultrasound probe will be used. No ultrasound study will be performed. The ultrasound gel will only be used to distend the vagina and improve the quality of MRI images; this is standard of practice in MRI for endometriosis and for several other gynecological diseases.

Eligibility

Sex: FEMALEMin age: 18 YearsMax age: 70 Years

Medical Language ↔ Plain English

Inclusion Criteria: \- Patients with clinical diagnosis of endometriosis, in any stage, candidate for diagnostic overtherapeutic laparoscopic surgery. Exclusion Criteria: * Subjects less than 18 years of age or greater than 70 years of age. * Any contraindication to MRI, including electrical implants, such as cardiac pacemakers or perfusion pumps. MRI non-compatible ferromagnetic implants such as aneurysm clips, surgical clips, prostheses, artificial hearts, prosthetic heart valves that are not compatible with the gradient maps of our scanners, metal fragments, shrapnel, metallic tattoos anywhere on the body, tattoos near the eye, steel implants, and/or ferromagnetic objects such as jewelry, or metal clips in clothing that cannot be removed. * History of claustrophobic reactions. * Individuals who do not speak or understand English since providing a translated version of the entire consent form is not practicable * Any contraindication to PET including active breastfeeding (a negative STAT quantitative serum hCG pregnancy test is required on the day of the scan before the subject can participate) * History of research-related radiation exposure exceeding current Radiology Department guidelines (i.e., 50 mSv in the prior 12 months). * QTc\>460msec obtained within 30 days from the PET/MR * eGFR \<60mL/min/1.73m2 obtained within 30 days from the PET/MR * AST \>40U/L and/or ALT \>55 U/L obtained within 30 days from the PET/MR * A greater risk than normal for potential cardiac arrest such as history of non compensated congestive heart failure, poorly controlled arrythmias, symptomatic non compensated cardiopathies. * History of major head trauma (i.e., multiple concussions, traumatic brain injury). * History of bleeding disorders. * Inability to lie comfortably on a bed inside the PET/MRI bore as assessed by physical examination and medical history (e.g., back pain, severe arthritis). * Subjects under the direct supervision of the principal investigator. * Body weight of \> 300 lbs. (weight limit of the MRI table) or BMI \>33.0 per the standard operating procedure of PET/MRI safety at the Martinos Center. * Subjects from any other at-risk populations (e.g., children and minors cognitively impaired persons, prisoners).

Outcomes

Primary Outcomes

Diagnostic Accuracy of PET/MR in Preoperative Endometriosis Detection

To determine the accuracy, sensitivity, and specificity of \[18F\]-FAPI-74 and/or \[68Ga\]CBP8 PET/MRI in detecting and classifying endometriosis, using the gold standard methods as the reference.

Time frame: 1-2 Months

Diagnostic Performance of PET/MRI vs. Conventional Imaging

To determine the accuracy, sensitivity, and specificity of \[18F\]-FAPI-74 or \[68Ga\]CBP8-PET/MR images versus stand-alone wholebody MRI and/or pelvic MRI and/or ultrasound and/or computed tomography in pre-operative patients with suspected endometriosis lesion.

Time frame: 1-2 Months

Secondary Outcomes

Impact of [18F]-FAPI-74 and [68Ga]CBP8 PET/MRI on Diagnosis and Management in Endometriosis

To determine if imaging with \[18F\]-FAPI-74 and/or \[68Ga\]CBP8 PET/MRI results in changes to diagnosis, medical or surgical management in endometriosis patients

Time frame: 1-6 months

Correlation of Pre-Treatment PET Uptake and Post-Treatment Response in Endometriosis

To determine if pre-treatment measures of \[18F\]-FAPI-74 and/or \[68Ga\]CBP8 standardized uptake values (SUVs) are correlated to post-treatment response in patients with endometriosis.

Time frame: 6-12 months