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

Abstract

Our objective was to evaluate 18 F-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 5 18) and those with metastatic tumors (n 5 10). 18 F-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 18 F-FDG uptake on visual analysis. The maximum standardized uptake value (SUVmax) ranged from 1.9 to 42 (mean 6 SD, 8.2 6 9.7; median, 4.6) in nonmetastatic tumors and 2.3 to 29.3 (mean 6 SD, 9.7 6 8.4; median, 7.4) in metastatic tumors. No statistical difference was observed between the groups (P 5 0.44), but succinate dehydrogenase-related tumors were notable in being the most 18 F-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 5 0.02). 18 F-FDG PET was superior to 131 I-metaiodobenzylguanidine in all metastatic patients but one. By contrast, 18 F-FDG PET underestimated the extent of the disease, compared with 6-18 F-fluorodopa PET, in 5 patients with metastatic pheochromocytoma. However, succinate dehydrogenase mutations (germline and somatic) and functional dedifferentiation do not adequately explain 18 F-FDG uptake since most tumors were highly avid for 18 F-FDG. Conclusion: 18 F-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.

Role of 18F-FDG PET/CT, 123I-MIBG SPECT, and CT in Restaging Patients Affected by Malignant Pheochromocytoma

“…In all patients, we found a full correspondence between the number of lesions revealed by radiologic imaging (CT) and the pathological uptakes revealed by 18 F-FDG PET/CT. The majority of the ambiguous lesions revealed by CT were confirmed as positive on 18 F-FDG PET/CT; our findings are quite similar to what was observed in other studies about PH [7,8,13,14] confirming 18 F-FDG PET/CT accuracy even in restaging and follow-up. Other studies have also demonstrated that 18 F-FDG PET/CT is superior to 123 I-MIBG SPECT for evaluating treatment response, considering its more accurate spatial resolution and the possible presence of MIBG-confounding treatment [19,20].…”

“…The role of 18 F-FDG PET/CT in staging patients affected by PH is well established as these tumors have shown high glucose metabolism [9][10][11][12][13][14][15][16], although, unfortunately, a correlation between 18 F-FDG uptake and malignant potential or prognosis has never been demonstrated [7,8]. In particular, a study reported that there is not a significant difference between 18 F-FDG uptake in benign and malignant PH and that the uptake is not influenced by the secretory status [17].…”

“…These possibilities could explain why 18 F-FDG avidity of PH seems to be different from other neuroendocrine tumors in which 18 F-FDG uptake seems to be related to tumor aggressiveness. A definite answer to this question has not been found yet, although an interesting study hypothesized that the amount of glucose uptake in chromaffin-derived tumors results from the severe impairment of oxidative phosphorylation in tumor cells [8]. Relatively few studies about restaging, follow-up, and treatment response monitoring have been performed, since the majority of studies comparing 18 F-FDG PET/CT and 123 I-MIBG SPECT either to MRI [10], 18 F-DOPA PET/CT [9,12], or CT are about diagnosis and detection of metastases.…”

“…Diagnosis is based on clinical data, laboratory findings, anatomical imaging [magnetic resonance imaging (MRI) and computed tomography (CT)], and functional imaging such as 123 I-metaiodobenzylguanidine single photon emission tomography ( 123 I-MIBG) SPECT and 18 F-fluorodeoxyglucose ( 18 F-FDG) positron emission tomography (PET)/CT. In particular, some studies, comparing both modalities, demonstrated that 18 F-FDG PET/CT has a higher sensitivity and specificity than 123 I-MIBG SPECT for detecting PH, even if a direct relationship between malignancy and 18 F-FDG uptake cannot be demonstrated [7,8]. Another possible application for 123 I-MIBG and 18 F-FDG PET/CT is the evaluation of a possible 131 I-MIBG radiometabolic treatment, which can be the only therapeutic option in cases where surgical resection is not possible.…”

Vasovagal-related stress immediately before FDG injection may increase bilateral adrenal FDG uptake

“…Differential diagnoses for bilateral avid adrenal FDG uptake other than metastasis include malignant lymphoma, 13 pheochromocytoma, 14 adrenal hyperplasia causing Cushing's syndrome, 15 adrenal tuberculosis, 16 adrenal histoplasmosis, 17 adrenal haemorrhage 18 and adrenal myelolipoma. 19 However, these diseases except mild hyperplasia may exhibit clear morphological abnormalities.…”