¹⁸F-FDG Avidity of Pheochromocytomas and Paragangliomas: A New Molecular Imaging Signature?

¹ Service Central de Biophysique et de Médecine Nucléaire, Centre Hospitalo-Universitaire de la Timone, Marseille, France
² Service de Chirurgie Générale et Endocrinienne, Centre Hospitalo-Universitaire de la Timone, Marseille, France
³ Laboratoire de Biochimie et Biologie Moléculaire, Centre Hospitalier Universitaire Conception, Marseille, France
⁴ Service d'Endocrinologie, Diabète et Métabolismes, Centre Hospitalo-Universitaire de la Timone, Marseille, France
⁵ Service D'oto-Rhino-Laryngologie, Centre Hospitalo-Universitaire de la Timone, Marseille, France
⁶ Faculté de Médecine, Institut National de la Santé et de la Recherche Médicale, Marseille, France

^* To whom correspondence should be addressed. E-mail: david.taieb{at}ap-hm.fr.

	Abstract

Our objective was to evaluate ¹⁸F-FDG PET uptake in patients with nonmetastatic and metastatic chromaffin-derived tumors. Methods: Twenty-eight consecutive unrelated patients with chromaffin tumors, including 9 patients with genetically determined disease, were studied. A combination of preoperative imaging work-up, surgical findings, and pathologic analyses was used to classify the patients into 2 groups: those with nonmetastatic disease (presumed benign, n = 18) and those with metastatic tumors (n = 10). ¹⁸F-FDG PET was performed in all cases. Visual and quantitative analyses were individually graded for each tumor. Somatic mutations of the succinate dehydrogenase subunits B and D and Von-Hippel Lindau genes were also evaluated in 6 benign sporadic tumor samples. Results: All but 2 patients showed significantly increased ¹⁸F-FDG uptake on visual analysis. The maximum standardized uptake value (SUVmax) ranged from 1.9 to 42 (mean ± SD, 8.2 ± 9.7; median, 4.6) in nonmetastatic tumors and 2.3 to 29.3 (mean ± SD, 9.7 ± 8.4; median, 7.4) in metastatic tumors. No statistical difference was observed between the groups (P = 0.44), but succinate dehydrogenase–related tumors were notable in being the most ¹⁸F-FDG–avid tumors (SUVmax, 42, 29.3, 21, 17, and 5.3). Succinate dehydrogenase and Von-Hippel Lindau–related tumors had a significantly higher SUVmax than did neurofibromatosis type 1 and multiple endocrine neoplasia type 2A syndrome–related tumors (P = 0.02). ¹⁸F-FDG PET was superior to ¹³¹I-metaiodobenzylguanidine in all metastatic patients but one. By contrast, ¹⁸F-FDG PET underestimated the extent of the disease, compared with 6-¹⁸F-fluorodopa PET, in 5 patients with metastatic pheochromocytoma. However, succinate dehydrogenase mutations (germline and somatic) and functional dedifferentiation do not adequately explain ¹⁸F-FDG uptake since most tumors were highly avid for ¹⁸F-FDG. Conclusion: ¹⁸F-FDG PET positivity is almost a constant feature of pheochromocytomas and paragangliomas. It may be considered a molecular signature of such tumors, although which aspect of the plethora of molecular changes associated with dedifferentiation, germline genetic defects, or the adaptive response to hypoxia is responsible for this characteristic requires further elucidation.

Key Words: molecular imaging, PET/CT, neuroendocrine, FDG PET, pheochromocytoma, Warburg effect

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