Molecular Imaging Advances in Endometriosis: The Promise of Radiopharmaceuticals

Endometriosis is a highly prevalent, chronic gynecological disorder characterized by the ectopic presence of endometrial-like tissue, driving significant morbidity and chronic pelvic pain. Pathologically, it is increasingly recognized as a fibro-inflammatory condition involving extensive tissue remodeling and fibrosis. Current conventional imaging modalities, including ultrasound and MRI, are primarily morphological, while standard molecular imaging using Positron Emission Tomography (PET) tracers has shown limited diagnostic utility. [¹⁸F]Fluorodeoxyglucose (FDG) suffers from high physiological uptake in pelvic organs and inconsistent detection of lesions. Receptor-based tracers like [⁶⁸Ga]Ga-DOTATATE have demonstrated uncertain efficacy. In contrast, radiopharmaceuticals targeting the Fibroblast Activation Protein (FAP) offer a promising molecular approach. FAP is specifically overexpressed by activated fibroblasts present in the stroma of endometriotic lesions, correlating significantly with tissue fibrosis (collagen content) and local immune infiltration (e.g., CD68 macrophages). This comprehensive review analyzes the landscape of radiopharmaceuticals for endometriosis imaging, contrasting the specific limitations of traditional metabolic and receptor agents with the molecular rationale and emerging evidence supporting the use of FAP Inhibitors (FAPI), positioning them as crucial, non-invasive tools for the future diagnosis and management of this challenging disease.