Clinical trial NCT06377553: PET/MRI for Evaluation of Endometriosis
Official title: PET/MRI Evaluation of Endometriosis Using Intercellular Matrix Radiopharmaceuticals
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: Endometriosis
Endometrioma
Keywords: Endometriosis
[18F]-FAPI-74
[68Ga]CBP8-PET
PET/MR
Fibrosis
DIE
Endometrioma
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
First posted: 2024-04-22
Enrollment: 60
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: In total, 60 subjects with clinically diagnosed endometriosis will be recruited. All subjects recruited for the study will be able to withdraw from the study at any time. The patients will be referred to the study by their treating physicians to investigate clinically diagnosed endometriosis. We will not recruit or enroll healthy volunteers in this study.

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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).

Primary outcomes:
measure: Diagnostic Accuracy of PET/MR in Preoperative Endometriosis Detection
timeFrame: 1-2 Months
measure: Diagnostic Performance of PET/MRI vs. Conventional Imaging
timeFrame: 1-2 Months
Secondary outcomes:
measure: Impact of [18F]-FAPI-74 and [68Ga]CBP8 PET/MRI on Diagnosis and Management in Endometriosis
timeFrame: 1-6 months
measure: Correlation of Pre-Treatment PET Uptake and Post-Treatment Response in Endometriosis
timeFrame: 6-12 months
Other outcomes:
Locations:
city: Charlestown
country: United States
facility: Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School
state: Massachusetts
Study officials:
affiliation: Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School
name: Onofrio Catalano
role: PRINCIPAL_INVESTIGATOR
References:
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