Prospective Trial of [18F]AlF-FAPI-74 for PET Imaging of Fibroblast Activation Protein in Patients With Endometriosis

• [18F]AlF-FAPI-74 PET/CT (Diagnostic test): A \[18F\]AlF-FAPI-74 PET/CT will be performed at UZ Leuven before the participant's planned laparoscopy. Participants are required to fast for 4 hours before tracer administration but water is allowed. An intravenous line will be placed and \[18F\]AlF-FAPI-74 will be administered in one bolus (3.5 MBq/kg). PET/CT acquisition will start after 60 minutes. The CT will be a low dose CT with oral contrast. If there are no contraindications, 20 mg Buscopan may be administered shortly before imaging to reduce bowel movement. Participants may optionally undergo an additional NeuroEXPLORER PET/CT scan on the same day after the same \[18F\]AlF-FAPI-74 administration, so no second tracer injection is required. Participants who start treatment with a GnRH (ant)agonist after their first scan may undergo a second \[18F\]AlF-FAPI-74 PET/CT to investigate changes in tracer uptake during hormonal treatment. Participants will be monitored for adverse events related to study procedures.
• [18F]AlF-FAPI-74 PET/CT (Diagnostic test): A \[18F\]AlF-FAPI-74 PET/CT will be performed at UZ Leuven before the participant's planned laparoscopy. Participants are required to fast for 4 hours before tracer administration but water is allowed. An intravenous line will be placed and \[18F\]AlF-FAPI-74 will be administered in one bolus (3.5 MBq/kg). PET/CT acquisition will start after 60 minutes. The CT will be a low dose CT with oral contrast. If there are no contraindications, 20 mg Buscopan may be administered shortly before imaging to reduce bowel movement. Participants may optionally undergo an additional NeuroEXPLORER PET/CT scan on the same day after the same \[18F\]AlF-FAPI-74 administration, so no second tracer injection is required. Participants will be monitored for adverse events related to study procedures.

Primary outcomes

• Evaluate diagnostic performance of [18F]AlF-FAPI-74 PET/CT as a non-invasive tool to diagnose deep infiltrating endometriosis and/or superficial peritoneal endometriosis, in comparison with laparoscopic findings in women with suspected endometriosis [From enrollment until laparoscopy (up to 1 month after the last [18F]AlF-FAPI-74 PET/CT)]: Correlating the locations of endometriotic lesions on \[18F\]AlF-FAPI-74 PET/CT and the locations of endometriotic lesions detected during laparoscopy.
• Frequency of serious adverse device effects (SADEs) related to NeuroEXPLORER PET/CT [From enrollment until laparoscopy (up to 1 month after the last NeuroEXPLORER PET/CT)]: The number of participants experiencing one or more serious adverse device effects (SADEs) during NeuroEXPLORER PET/CT will be recorded.

Secondary outcomes

• Sensitivity, specificity, positive and negative predictive value and accuracy of [18F]AlF-FAPI-74 PET/CT for detecting endometriosis [From enrollment until laparoscopy (up to 1 month after the last [18F]AlF-FAPI-74 PET/CT)]: Sensitivity, specificity, positive predictive value, negative predictive value, accuracy of \[18F\]AlF-FAPI-74 PET/CT in detecting endometriotic lesions using laparoscopic findings as the reference standard.
• Semi-quantitative uptake measurements [From enrollment until laparoscopy (up to 1 month after the last [18F]AlF-FAPI-74 PET/CT)]: Semi-quantitative uptake measurements (maximal standardized uptake value (SUVmax), average SUV (SUVmean), peak SUV (SUVpeak) of endometriotic lesions on \[18F\]AlF-FAPI-74 PET/CT.
• Lesion-to-background uptake values [From enrollment until laparoscopy (up to 1 month after the last [18F]AlF-FAPI-74 PET/CT)]: Endometriotic lesion-to-background uptake values (SUV lesion divided by SUV background) for \[18F\]AlF-FAPI-74 PET/CT, using following background organs: liver, lung, gluteus muscle, mediastinal bloodpool, bowel, bone marrow (L4 if no abnormal uptake).
• FAP-positive endometriotic burden [From enrollment until laparoscopy (up to 1 month after the last [18F]AlF-FAPI-74 PET/CT)]: Total FAP-positive endometriotic burden, defined as the sum of the volumes of all lesions deemed to be endometriotic in nature.
• Additional lesions after unblinding [From enrollment until laparoscopy (up to 1 month after the last [18F]AlF-FAPI-74 PET/CT)]: Number of additional endometriotic lesions recorded after unblinding of the surgeon during laparoscopy.
• Sensitivity, specificity, positive predictive value, negative predictive value and accuracy of MRI for detecting endometriosis [From enrollment until laparoscopy (up to 1 month after the last [18F]AlF-FAPI-74 PET/CT)]: Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of MRI in detecting endometriotic lesions, in patients in which MRI is available, and comparison with \[18F\]AlF-FAPI-74 PET/CT, laparoscopy and if available ultrasound.
• Sensitivity, specificity, positive predictive value, negative predictive value and accuracy of ultrasound for detecting endometriosis [From enrollment until laparoscopy (up to 1 month after the last [18F]AlF-FAPI-74 PET/CT)]: Sensitivity, specificity, positive predictive value, negative predictive value and accuracy of ultrasound in detecting endometriotic lesions, in patients in which ultrasound is available, and comparison with \[ 18F\]AlF-FAPI-74 PET/CT, laparoscopy and if available MRI.
• Number of participants with a change in clinical management following review of [18F]AlF-FAPI-74 PET/CT findings [From enrollment until laparoscopy (up to 1 month after the last [18F]AlF-FAPI-74 PET/CT)]: The number and proportion of participants with a change in planned clinical management attributable to the \[18F\]AlF-FAPI-74 PET/CT findings, as documented by the treating clinical team, will be recorded. The type of management change will also be documented.
• Patient-reported responses to a study-specific questionnaire on the psychological impact of [18F]AlF-FAPI-74 PET/CT [From enrollment until laparoscopy (up to 1 month after the last [18F]AlF-FAPI-74 PET/CT)]: Psychological impact of the \[18F\]AlF-FAPI-74 PET/CT procedure will be assessed using a study-specific questionnaire completed before and after the scan procedure. The questionnaire evaluates e.g. anxiety, concerns about the procedure, discomfort, or personnel. Responses will be scored according to the predefined questionnaire scoring system.
• Intra- and interreader agreement for detection and localization of endometriosis lesions on [18F]AlF-FAPI-74 PET/CT [From enrollment until laparoscopy (up to 1 month after the last [18F]AlF-FAPI-74 PET/CT)]: Two PET readers will independently identify and localize suspicious endometriosis lesions on \[18F\]AlF-FAPI-74 PET/CT. Intra- and interobserver agreement will be determined using the GWET agreement coefficient (AC) or intraclass correlation coefficients (ICC).
• Adverse events [From tracer administration until 30 days after tracer administration]: Adverse events associated with \[18F\]AlF-FAPI-74 PET/CT.
• FAP IHC correlation [From enrollment until laparoscopy (up to 1 month after the last [18F]AlF-FAPI-74 PET/CT)]: Correlation of \[18F\]AlF-FAPI-74 biodistribution with FAP tissue expression as measured by immunohistochemistry (IHC).
• Change in [18F]AlF-FAPI-74 PET/CT findings after initiation of GnRH therapy [From enrollment until laparoscopy (up to 1 month after the last [18F]AlF-FAPI-74 PET/CT)]: Evolution of \[18F\]AlF-FAPI-74 PET/CT scans in patients initiating GnRH-agonist or GnRH-antagonist medication and receiving 2 \[18F\]AlF-FAPI-74 PET/CT (prior and post initiation of GnRH-agonist or GnRH-antagonist medication): (i) number of lesion; (ii) uptake; (iii) endometriotic lesion-to-background value; (iv) correlation with laparoscopy and if available MRI and/or ultrasound.
• Frequency of adverse device effects (ADEs) associated with NeuroEXPLORER PET/CT [From enrollment until laparoscopy (up to 1 month after the last NeuroEXPLORER PET/CT)]: The number of participants experiencing one or more adverse device effects (ADEs) during NeuroEXPLORER PET/CT will be recorded.
• Patient Reported Outcome Measures (PROM) to capture the perspective and satisfaction of the NeuroEXPLORER PET/CT [From enrollment until laparoscopy (up to 1 month after the last NeuroEXPLORER PET/CT)]: Patient Reported Outcome Measures (PROM) to capture the perspective and satisfaction of the NeuroEXPLORER PET/CT. This will be scored on a 0-10 Likert scale on the dimensions of "Investigation smoothness", "satisfaction with the scanning procedure" and "comfortable positioning during the examination".

Other outcomes

• Number of endometriotic lesions detected on NeuroEXPLORER PET/CT compared with standard [18F]AlF-FAPI-74 PET/CT [From enrollment until laparoscopy (up to 1 month after the last [18F]AlF-FAPI-74 PET/CT)]: The number of endometriotic lesions detected on NeuroEXPLORER PET/CT will be compared with the number detected on the corresponding standard \[18F\]AlF-FAPI-74 PET/CT acquisition obtained after the same tracer injection. Results will be summarized descriptively.

Sex: Female, ages: 18 Years to 64 Years

Inclusion Criteria:

* Voluntary written informed consent of the participant has been obtained prior to any screening procedures.
* At least 18 years of age at the time of signing the Informed Consent Form (ICF).
* At least one of the following to be eligible for the DE cohort: (i) Clinical suspicion of DE, defined as the presence of deep nodule(s) during vaginal examination determined by a clinician who is an expert in endometriosis. (ii) Diagnostic suspicion of DE, defined as an ultrasound and/or MRI that shows lesions suspicious for DE.
* At least one of the following to be eligible for the SPE cohort: (i) Clinical suspicion of SPE, defined as clinical symptoms suspicious of SPE determined by a clinician who is an expert in endometriosis. These clinical symptoms include dysmenorrhea, deep dyspareunia, dysuria, dyschezia, painful rectal bleeding or haematuria, shoulder tip pain, catamenial pneumothorax, cyclical cough/haemoptysis/chest pain, cyclical scar swelling and pain, fatigue, and infertility. (ii) Diagnostic suspicion of SPE, defined as an ultrasound and/or MRI that shows lesions suspicious for SPE.
* Planned laparoscopy for suspected endometriosis.

Exclusion Criteria:

* For SPE cohort: (i) Ultrasound and/or MRI with lesions suspicious of ovarian endometriosis and/or DE. (ii) Clinical symptoms suspicious of ovarian endometriosis and/or DE, determined by a clinician who is an expert in endometriosis.
* Prior abdominal surgery less than one year ago.
* Female who is pregnant, breastfeeding or is of childbearing potential and not using an adequate, highly effective contraceptive or no usage of contraception when sexually active are not accepted.
* Participant is mentally or legally incapacitated, does not understand the study design or is not willing or capable to undergo all study-specific procedures.
* Any disorder or condition, which in the Investigator's opinion might jeopardise the participant's safety or compliance with the protocol, or may influence the result of the study.
* Any prior or concomitant treatment(s) that might jeopardise the participant's safety or that would compromise the integrity of the Trial.
* Participation in an interventional Trial with an investigational medicinal product (IMP) or device when the trial designs are not considered compatible by the study team.
* Participation in a clinical scientific study in the last 12 months with a radiation exposure caused by the experimental procedures greater than 1 mSv.
* Participant has a known hypersensitivity to \[18F\]AlF-FAPI-74 or the used excipients.

• Study Protocol and Statistical Analysis Plan (PDF, 2026-07-09)