18F-FDOPA PET/CT Imaging of MAX-Related Pheochromocytoma

J Clin Endocrinol Metab. 2018 Apr 1;103(4):1574-1582. doi: 10.1210/jc.2017-02324.


Context: MYC-associated factor X (MAX) has been recently described as a new susceptibility pheochromocytoma (PHEO) gene with a total of ~40 reported cases. At present, no study has specifically described the functional imaging phenotype of MAX-related PHEO.

Objective, patients, and design: The objective of the present study was to present our experience with contrast-enhanced computed tomography (CT) and 18F-fluorodihydroxyphenylalanine (18F-FDOPA) positron emission tomography (PET)/CT in six consecutive patients (four at the initial diagnosis and two at the follow-up evaluation) with rare, but clinically important, MAX-related PHEOs. In five patients, 18F-FDOPA was also compared with other radiopharmaceutical agents.

Results: The patients had five different mutations in the MAX gene that caused disruption of Max/Myc interaction and/or abolished interaction with DNA based on in silico analyses. All but one patient developed bilateral PHEOs during their lifetime. In all cases, 18F-FDOPA PET/CT accurately visualized PHEOs that were often multiple within the same gland or bilaterally and detected more adrenal and extra-adrenal lesions than did CT (per-lesion sensitivity, 90.9% vs 52.4% for CT/magnetic resonance imaging). The two PHEOs missed on 18F-FDOPA PET/CT were <1 cm, corresponding to nodular adrenomedullary hyperplasia. 68Ga-DOTA,Tyr3-octreotate PET/CT detected fewer lesions than did 18F-FDOPA PET/CT in one of three patients, and 18F-fluorodeoxyglucose PET/CT was only faintly positive in two of four patients with underestimation of extra-adrenal lesions in one patient.

Conclusions: MAX-related PHEOs exhibit a marked 18F-FDOPA uptake, a finding that illustrates the common well-differentiated chromaffin pattern of PHEOs associated with activation of kinase signaling pathways. 18F-FDOPA PET/CT should be considered as the first-line functional imaging modality for diagnostic or follow-up evaluations for these patients.

Trial registration: ClinicalTrials.gov NCT00004847.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adrenal Gland Neoplasms / diagnostic imaging*
  • Adrenal Gland Neoplasms / genetics
  • Adrenal Gland Neoplasms / pathology
  • Adult
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / genetics*
  • Dihydroxyphenylalanine / analogs & derivatives
  • Female
  • Humans
  • Male
  • Middle Aged
  • Mutation
  • Pheochromocytoma / diagnostic imaging*
  • Pheochromocytoma / genetics
  • Pheochromocytoma / pathology
  • Positron Emission Tomography Computed Tomography / methods*
  • Young Adult


  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • MAX protein, human
  • fluorodopa F 18
  • Dihydroxyphenylalanine

Associated data

  • ClinicalTrials.gov/NCT00004847