title: Functional characterization of nonmetastatic paraganglioma and pheochromocytoma by (18) F-FDOPA PET: focus on missed lesions.
abstract: OBJECTIVE
  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).
  
  
  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. (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.
  
  
  CONCLUSIONS
  (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.
authors.affiliation: Department of Nuclear Medicine, La Timone University Hospital, CERIMED, Aix-Marseille University, Marseille, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Gabriel
authors.forename: Elise M
authors.initials: EM
authors.lastname: Blanchet
authors.forename: Frédéric
authors.initials: F
authors.lastname: Sebag
authors.forename: Clara C
authors.initials: CC
authors.lastname: Chen
authors.forename: Nicolas
authors.initials: N
authors.lastname: Fakhry
authors.forename: Arnaud
authors.initials: A
authors.lastname: Deveze
authors.forename: Anne
authors.initials: A
authors.lastname: Barlier
authors.forename: Isabelle
authors.initials: I
authors.lastname: Morange
authors.forename: Karel
authors.initials: K
authors.lastname: Pacak
authors.forename: David
authors.initials: D
authors.lastname: Taïeb
mesh_terms: D000008:Abdominal Neoplasms / Q000000981:diagnostic imaging; D000310:Adrenal Gland Neoplasms / Q000000981:diagnostic imaging* / Q000235:genetics; D004295:Dihydroxyphenylalanine / Q000031:analogs & derivatives*; D005188:False Negative Reactions; D006258:Head and Neck Neoplasms / Q000000981:diagnostic imaging; D006801:Humans; D010235:Paraganglioma / Q000000981:diagnostic imaging* / Q000235:genetics; D010673:Pheochromocytoma / Q000000981:diagnostic imaging* / Q000235:genetics; D049268:Positron-Emission Tomography; D012189:Retrospective Studies; D013385:Succinate Dehydrogenase / Q000235:genetics
chemical_list: C043437:fluorodopa F 18; D004295:Dihydroxyphenylalanine; D013385:Succinate Dehydrogenase