Functional characterization of nonmetastatic paraganglioma and pheochromocytoma by 18F-FDOPA PET: focus on missed lesions

Aims and methods To evaluate the clinical value of F-18-fluorodihydroxyphenylalanine (F-18-FDOPA) PET in relation to tumour localization and the patient's genetic status in a large series of pheochromocytoma/paraganglioma (PHEO/PGL) patients and to discuss in detail false-negative results. A retrospective study of PGL patients who were investigated with F-18-FDOPA PET or PET/CT imaging in two academic endocrine tumour centres was conducted (La Timone University Hospital, Marseilles, France and National Institutes of Health (NIH), Bethesda, MD, USA). Results One hundred sixteen patients (39.7% harbouring germline mutations in known disease susceptibility genes) were evaluated for a total of 195 PHEO/PGL foci. F-18-FDOPA PET correctly detected 179 lesions (91.8%) in 107 patients (92.2%). Lesion-based sensitivities for parasympathetic PGLs (head, neck, or anterior/middle thoracic ones), PHEOs, and extra-adrenal sympathetic (abdominal or posterior thoracic) PGLs were 98.2% [96.5% for Timone and 100% for NIH], 93.9% [93.8 and 93.9%] and 70.3% [47.1 and 90%] respectively (P < 0.001). Sympathetic (adrenal and extra-adrenal) SDHx-related PGLs were at a higher risk for negative F-18-FDOPA PET than non-SDHx-related PGLs (14/24 vs 0/62, respectively, P < 0.001). In contrast, the risk of negative F-18-FDOPA PET was lower for parasympathetic PGLs regardless of the genetic background (1/90 in SDHx vs 1/19 in non-SDHx tumours, P = 0.32). F-18-FDOPA PET failed to detect two head and neck PGLs (HNPGL), likely due to their small size, whereas most missed sympathetic PGL were larger and may have exhibited a specific F-18-FDOPA-negative imaging phenotype. F-18-FDG PET detected all the missed sympathetic lesions. Conclusions F-18-FDOPA PET appears to be a very sensitive functional imaging tool for HNPGL regardless of the genetic status of the tumours. Patients with false-negative tumours on F-18-FDOPA PET should be tested for SDHx mutations.