Diagnostic Accuracy of [18F]AlF‑FAPI‑74 PET/CT for Detecting Deep Infiltrating and Superficial Peritoneal Endometriosis in Suspected Patients

The primary objective is to assess the diagnostic performance of non‑invasive [18F]AlF-FAPI-74 PET/CT for detection of endometriosis by comparison with laparoscopy, the current standard invasive diagnostic procedure, in patients suspected of deep infiltrating or superficial peritoneal disease.

The trial enrolled female participants aged 18 years and older who were scheduled for laparoscopy due to a clinical or imaging suspicion of deep infiltrating or superficial peritoneal endometriosis. Selection required voluntary written informed consent and confirmation of either a clinician‑determined suspicion (e.g., deep nodules on examination or symptoms such as dysmenorrhea, dyspareunia, dysuria, dyschezia, infertility) or imaging findings (ultrasound or MRI) suggestive of disease. General health status was not otherwise restricted, and no specific lifestyle criteria (diet, physical activity, habits) were stipulated. The sponsor did not provide information on the total number of participants.

The study is a prospective, phase IV diagnostic trial evaluating the performance of [18F]AlF‑FAPI‑74 PET/CT for detecting deep infiltrating and superficial peritoneal endometriosis compared with intra‑operative laparoscopy, the reference standard. After obtaining written informed consent, participants undergo a screening visit to confirm eligibility criteria, including clinical or imaging suspicion of disease and scheduled laparoscopy. Eligible subjects receive a single intravenous administration of 600 MBq [18F]AlF‑FAPI‑74 followed by PET/CT imaging; Buscopan 20 mg IV is administered as needed to reduce gastrointestinal motion. The PET/CT scan is performed within a predefined time window before the planned laparoscopic procedure, which serves as the primary comparator visit. A postoperative visit records surgical findings, adverse events, and any additional lesions identified after unblinding. For participants initiating GnRH‑agonist or GnRH‑antagonist therapy, a second PET/CT scan is performed after treatment initiation to assess longitudinal changes. The final end‑of‑study visit occurs after all imaging and surgical data are collected, typically within 4–6 weeks of the initial scan. Participant involvement therefore spans approximately 1–2 months from screening to study completion. Early termination may occur if a participant withdraws consent, experiences a serious adverse reaction to the investigational tracer, cannot undergo the scheduled laparoscopy, or if protocol‑defined safety criteria are met.

The investigational radiotracer [18F]AlF-FAPI-74 is supplied as a solution for injection and is administered at a activity of 600 MBq per participant. The dose is delivered by a single intravenous injection immediately prior to PET/CT imaging, with no repeat administrations planned during the study.

As an auxiliary medication, Buscopan 20 mg/1 ml solution for injection, containing the antispasmodic agent hyoscine butylbromide, is given intravenously at a dose of 20 mg shortly before the radiotracer injection to minimize gastrointestinal motion during image acquisition.

Dosing is performed in a controlled clinical setting under direct observation. The timing of each injection is recorded, and participants are monitored for vital signs and any adverse events for a minimum of 60 minutes post‑administration. Compliance with the administration protocol is verified through electronic case report forms and a drug accountability log.

Efficacy will be assessed by comparing the diagnostic performance of [18F]AlF‑FAPI‑74 PET/CT with intra‑operative laparoscopic findings, which serve as the reference standard for the detection of deep infiltrating and superficial peritoneal endometriosis. Correlation of lesion locations identified on PET/CT with those observed during laparoscopy will constitute the primary efficacy evaluation.

Secondary efficacy parameters include sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy of PET/CT for lesion detection. Semi‑quantitative uptake will be measured using maximal standardized uptake value (SUVmax), average SUV (SUVmean), and peak SUV (SUVpeak) for each endometriotic lesion. Lesion‑to‑background ratios will be calculated by dividing lesion SUV by background SUV values obtained from liver, lung, gluteus muscle, mediastinal blood pool, bowel, and bone marrow (L4 when appropriate). The total fibroblast activation protein‑positive endometriotic burden will be expressed as the summed volume of all PET‑positive lesions.

Additional assessments comprise the count of new lesions identified after surgeon unblinding, diagnostic performance of MRI and ultrasound (when available), impact on clinical management, psychological impact of the imaging procedure, intra‑ and inter‑observer reproducibility of PET/CT interpretation, and safety outcomes recorded as adverse events. Correlation of PET tracer biodistribution with FAP expression measured by immunohistochemistry will be performed on tissue samples obtained during laparoscopy.

For participants initiating GnRH‑agonist or GnRH‑antagonist therapy, two PET/CT scans (pre‑ and post‑treatment) will be obtained to evaluate changes in lesion number, uptake metrics, lesion‑to‑background values, and concordance with laparoscopy, MRI, or ultrasound.