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

To evaluate the clinical value of (18) F-fluorodihydroxyphenylalanine ((18) F-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 (18) F-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). One hundred sixteen patients (39·7% harbouring germline mutations in known disease susceptibility genes) were evaluated for a total of 195 PHEO/PGL foci. (18) F-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 (18) F-FDOPA PET than non-SDHx-related PGLs (14/24 vs 0/62, respectively, P < 0·001). In contrast, the risk of negative (18) F-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). (18) F-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 (18) F-FDOPA-negative imaging phenotype. (18) F-FDG PET detected all the missed sympathetic lesions. (18) F-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 (18) F-FDOPA PET should be tested for SDHx mutations.