Quantitative 18F-DOPA PET/CT in pheochromocytoma: the relationship between tumor secretion and its biochemical phenotype
18F-FDOPA illustrates the properties of uptake and storage of catecholamines in pheochromocytomas (PHEOs). Until now, the relationship between 18F-FDOPA quantitative parameters and a PHEO secretory profile has not been specifically evaluated.
Materials and methods
Fifty-six patients (56% females, median age: 47.5 yrs) with non-metastatic PHEO, evaluated by 18F-FDOPA PET/CT, were included in this retrospective study. Forty-five patients had negative genetic testing (80.4%); five patients (8.9%) had RET, two patients (3.6%) had SDHB, two had SDHD (3.6%), one patient (1.8%) had NF1, and one patient had a VHL (1.8%) mutation. Correlation between 18F-FDOPA metabolic parameters (tumor SUVmax, tumor SUVmean, tumor SUVmax/liver SUVmax, MTV 42%, total lesion uptake), urinary metanephrines (MNs), and plasma chromogranin A (CgA) were evaluated.
All patients had positive 18F-FDOPA PET/CT. On univariate analysis, there was a strong correlation between all metabolic parameters and urinary MNs and plasma chromogranin A (CgA). The highest correlations were observed between total lesion (TL) uptake and the value of urinary MNs regardless of their nature (p = 8.10−15 and r = 0.80) and between MTV 42% and plasma CgA levels (p = 2.10−9, r = 0.74). On multivariate analysis, the correlation of uptake parameters and CgA levels did not persist further due to the relation of CgA and tumor diameter. A correlation between TL uptake and the normetanephrine/metanephrine ratio (NMN/MN) was also found, a finding that was in accordance with in vitro studies, which were found to have a higher catecholamine content in epinephrine producing PHEOs.
This retrospective study shows a correlation between 18F-FDOPA uptake, especially using TL uptake, urinary MNs, and a PHEO biochemical phenotype. This illustrates that beyond its localization value, 18F-FDOPA PET further enables PHEO characterization at a specific metabolic level.
KeywordsPheochromocytomas · 18F-FDOPA · Radionuclide imaging · Genetics
The review did not receive any specific grant from any funding agency in the public, commercial, or not-for-profit sector.
Compliance with ethical standards
Disclosure of potential conflicts of interest
The authors have nothing to disclose.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.
Informed consent was obtained from all individual participants included in the study.
- 3.Timmers HJ, Chen CC, Carrasquillo JA, Whatley M, Ling A, Havekes B, et al. Comparison of 18F-Fluoro-L-DOPA, 18F-Fluoro-Deoxyglucose, and 18F-Fluorodopamine PET and 123I-MIBG Scintigraphy in the localization of Pheochromocytoma and Paraganglioma. J Clin Endocrinol Metab. 2009;94:4757–67.CrossRefPubMedPubMedCentralGoogle Scholar
- 5.Barollo S, Bertazza L, Watutantrige-Fernando S, Censi S, Cavedon E, Galuppini F, et al. Overexpression of L-type amino acid transporter 1 (LAT1) and 2 (LAT2): novel markers of Neuroendocrine Tumors. PLoS One. 2016;11:e0156044. https://doi.org/10.1371/journal.pone.0156044.CrossRefPubMedPubMedCentralGoogle Scholar
- 6.Treglia G, Cocciolillo F, de Waure C, Di Nardo F, Gualano MR, Castaldi P, et al. Diagnostic performance of 18F-dihydroxyphenylalanine positron emission tomography in patients with paraganglioma: a meta-analysis. Eur J Nucl Med Mol Imaging. 2012;39:1144–53. https://doi.org/10.1007/s00259-012-2087-y.CrossRefPubMedGoogle Scholar
- 7.Fiebrich HB, de Jong JR, Kema IP, Koopmans KP, Sluiter W, Dierckx RA, et al. Total 18F-dopa PET tumour uptake reflects metabolic endocrine tumour activity in patients with a carcinoid tumour. Eur J Nucl Med Mol Imaging. 2011;38:1854–61. https://doi.org/10.1007/s00259-011-1862-5.CrossRefPubMedPubMedCentralGoogle Scholar
- 9.Eisenhofer G, Huynh TT, Elkahloun A, Morris JC, Bratslavsky G, Linehan WM, et al. Differential expression of the regulated catecholamine secretory pathway in different hereditary forms of pheochromocytoma. Am J Physiol Endocrinol Metab. 2008;295:E1223–33. https://doi.org/10.1152/ajpendo.90591.2008.CrossRefPubMedPubMedCentralGoogle Scholar