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

Abstract

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.

• Authors: David Taïeb, Abhishek Jha, Carole Guerin, Ying Pang, Karen T Adams, Clara C Chen, Pauline Romanet, Philippe Roche, Wassim Essamet, Alexander Ling, Martha M Quezado, Frédéric Castinetti, Fréderic Sebag, Karel Pacak
• Journal: The Journal of clinical endocrinology and metabolism (J Clin Endocrinol Metab) Vol. 103 Issue 4 Pg. 1574-1582 (04 01 2018) ISSN: 1945-7197 [Electronic] United States
• PMID: 29534198 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

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

Topics

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