Diagnostic Value of CXCR4-targeted PET/CT in ACTH-dependent and Independent Cushing's Syndrome

In previous clinical practice, 68Ga-Pentixafor PET/CT has demonstrated promising diagnostic utility in various neuroendocrine tumors by targeting CXCR4, a chemokine receptor overexpressed in several ACTH-secreting neoplasms. Building on this, and leveraging the Nuclear Medicine expertise at Peking Union Medical College Hospital, we aim to conduct a prospective observational study investigating the role of CXCR4-targeted PET/CT imaging in patients with confirmed or suspected Cushing's syndrome. This study will focus on evaluating the capability of \^68Ga-Pentixafor PET/CT to assist in the differential diagnosis of ACTH-dependent and ACTH-independent subtypes, as well as in the localization of primary lesions in challenging cases. Imaging performance will be assessed in comparison with conventional modalities and/or 68Ga-DOTATATE PET/CT when available.

Inclusion Criteria: * Clinical suspicion or confirmed diagnosis of Cushing's syndrome, based on clinical features (e.g., central obesity, moon face, muscle weakness) and/or abnormal cortisol-related biochemical tests. * Able and willing to undergo PET/CT imaging with both 68Ga-Pentixafor and, when applicable, 68Ga-DOTATATE. * Willing to provide informed consent for participation in the study. Exclusion Criteria: * Prior administration of therapeutic or investigational radiopharmaceuticals within 5 physical half-lives before study imaging. Pregnancy or breastfeeding. * History of allergic reaction to gallium-based tracers or related compounds. * Clinically unstable condition or severe organ dysfunction that, in the investigator's opinion, would interfere with PET/CT imaging or study participation. * Inability to complete both 68Ga-Pentixafor and, when applicable, 68Ga-DOTATATE PET/CT imaging due to clinical or logistical reasons.