Staging and Functional Characterization of Pheochromocytoma and Paraganglioma by 18F-Fluorodeoxyglucose (18F-FDG) Positron Emission Tomography

Timmers, Henri J L M; Chen, Clara C.; Carrasquillo, Jorge A.; Whatley, Millie; Ling, Alexander; Eisenhofer, Graeme; King, Kathryn S.; Rao, Jyotsna U.; Wesley, Robert; Adams, Karen T.; Pacák, Karel

doi:10.1093/jnci/djs188

Cited by 245 publications

(157 citation statements)

References 29 publications

Supporting

Mentioning

142

Contrasting

Unclassified

Order By: Relevance

“…However, the utility of 123 I-MIBG needs further evaluation. 18 F-FDG is currently the radiopharmaceutical of choice in metastatic PPGL (22)(23)(24) and has good accuracy, especially in patients with more dedifferentiated tumors and underlying SDHB mutations (20,25). These tumors show upregulated expression of glucose transporters as well as an upregulation of hexokinase, which explains the high 18 F-FDG uptake in tumors with SDH subunit A-D (collectively SDHx) deficiency (26,27).…”

Section: Discussionmentioning

confidence: 99%

Functional Imaging Signature of Patients Presenting with Polycythemia/Paraganglioma Syndromes

et al. 2017

Self Cite

View full text Add to dashboard Cite

Pheochromocytoma/paraganglioma (PPGL) syndromes associated with polycythemia have previously been described in association with mutations in the von Hippel-Lindau gene. Recently, mutations in the prolyl hydroxylase gene (PHD) 1 and 2 and in the hypoxiainducible factor 2 a (HIF2A) were also found to be associated with multiple and recurrent PPGL. Such patients also presented with PPGL and polycythemia, and later on, some presented with duodenal somatostatinoma. In additional patients presenting with PPGL and polycythemia, no further mutations have been discovered. Because the functional imaging signature of patients with PPGLpolycythemia syndromes is still unknown, and because these tumors (in most patients) are multiple, recurrent, and metastatic, the goal of our study was to assess the optimal imaging approach using 4 different PET radiopharmaceuticals and CT/MRI in these patients. Methods: Fourteen patients (10 women, 4 men) with confirmed PPGL and polycythemia prospectively underwent 68 Ga-DOTATATE (13 patients), 18 F-FDG (13 patients), 18 F-fluorodihydroxyphenylalanine ( 18 F-FDOPA) (14 patients), 18 F-fluorodopamine ( 18 F-FDA) (11 patients), and CT/MRI (14 patients). Detection rates of PPGL lesions were compared between all imaging studies and stratified between the underlying mutations. Results: 18 F-FDOPA and 18 F-FDA PET/CT showed similar combined lesion-based detection rates of 98.7% (95% confidence interval [CI], 92.7%-99.8%) and 98.3% (95% CI, 90.9%-99.7%), respectively. The detection rates for 68 Ga-DOTATATE (35.3%; 95% CI, 25.0%-47.2%), 18 F-FDG (42.3; 95% CI, 29.9%-55.8%), and CT/MRI (60.3%; 95% CI, 48.8%-70.7%) were significantly lower (P , 0.01), irrespective of the mutation status. Conclusion: 18 F-FDOPA and 18 F-FDA are superior to 18 F-FDG, 68 Ga-DOTATATE, and CT/MRI and should be the radiopharmaceuticals of choice in this rare group of patients.

show abstract

Section: Discussionmentioning

confidence: 99%

Functional Imaging Signature of Patients Presenting with Polycythemia/Paraganglioma Syndromes

et al. 2017

Self Cite

View full text Add to dashboard Cite

show abstract

“…Kaji et al showed that 18 F-fluorodihydroxyphenylalanine PET is superior to 123 I-MIBG scintigraphy in the context of von HippelLindau syndrome (26). We have previously shown that 18 F-FDG PET can distinguish between PPGLs with different underlying genotypes, and sensitivity of 18 F-FDG PET is higher in SDHB/Drelated PPGLs than non-SDHB/D-related metastatic PPGLs (92% vs. 37%) (38). The sensitivity of 123 I-MIBG scintigraphy appears to be lower in VHL-and SDHB-related PPGLs (22,25,26).…”

Section: Discussionmentioning

confidence: 93%

Semiquantitative ¹²³I-Metaiodobenzylguanidine Scintigraphy to Distinguish Pheochromocytoma and Paraganglioma from Physiologic Adrenal Uptake and Its Correlation with Genotype-Dependent Expression of Catecholamine Transporters

et al. 2015

Self Cite

View full text Add to dashboard Cite

123 I-metaiodobenzylguanidine ( 123 I-MIBG) scintigraphy plays an important role in the diagnostic evaluation of patients with pheochromocytoma and paraganglioma (PPGL). 123 I-MIBG targets cell membrane and vesicular catecholamine transporters of chromaffin cells and facilitates localization of the primary tumor and metastatic lesions. Its specificity for the diagnosis of adrenomedullary chromaffin cell tumors can be jeopardized by physiologic uptake by the normal adrenal medulla. The aim of this study was to distinguish between PPGLs and normal adrenal glands by evaluating semiquantitative 123 I-MIBG uptake and to examine genotype-specific differences in correlation with expression of catecholamine transporter systems. Methods: Sixty-two PPGLs collected from 57 patients with hereditary mutations in SDHA (n 5 1), SDHB (n 5 2), and SDHD (n 5 4) (SDH is succinate dehydrogenase); von Hippel-Lindau (VHL; n 5 2); RET (n 5 12); neurofibromin 1 (NF1; n 5 2); and MYC-associated factor X (MAX; n 5 1), and with sporadic PPGLs (n 5 33) were investigated. Preoperative planar and SPECT images were semiquantitatively analyzed using uptake measurements. Tumor-to-liver and normal adrenal-to-liver ratios were calculated and correlated with clinical characteristics including genotype, tumor size, and plasma metanephrines concentrations. The expression of norepinephrine transporter (NET) and vesicular monoamine transporter (VMAT-1) was evaluated immunohistochemically in paraffin-embedded tumor tissues. Results: Mean tumor-to-liver ratios of PPGL lesions were significantly higher than normal adrenal-to-liver ratios (P , 0.001). Cutoff values to distinguish between physiologic and pathologic adrenal uptake were established at 0.7 (100% sensitivity, 10.3% specificity) and 4.3 (100% specificity, 66.1% sensitivity). No statistically significant differences in 123 I-MIBG uptake were found across PPGLs of different genotypes. Mean NET expression in hereditary cluster 2 (RET, NF1, MAX) and apparently sporadic tumors was significantly higher than for hereditary cluster 1 (SDHx, VHL) PPGLs (P 5 0.011 and 0.006, respectively). Mean VMAT-1 expression in hereditary cluster 1 PPGLs was significantly higher than for cluster 2 tumors (P 5 0.010). 123 I-MIBG uptake significantly correlated with maximum tumor diameter (P 5 0.002). 123 I-MIBG uptake, however, did not correlate with either NET or VMAT-1 expression. Conclusion: Liver-normalized semiquantitative 123 I-MIBG uptake may be helpful to distinguish between pheochromocytoma and physiologic adrenal uptake. Genotype-specific differences in the expression of NET and VMAT-1 do not translate into differences in 123 I-MIBG uptake.

show abstract

“…The 18 F-FDG uptake reflects glucose uptake and behaves as an analog of glucose, its distribution closely follows that of glucose-metabolizing cells and organs but with some differences. The 18 F-FDG enters cells by membrane Glucose Transporters (GLUTs) then undergoes phosphorylation by hexokinase to form 18 FDG-6-phosphate [5,6], unlike glucose, this undergoes further enzymatic reactions and is effectively trapped into the cell. Increased uptake of 18 F-FDG is not specific to paragangliomas, however, most paragangliomas are avid for F 18 FDG despite their relative indolence [5,6].…”

Section: Discussionmentioning

confidence: 99%

False Positive or False Negative PET Scan?

Azad¹

2017

CSMC

View full text Add to dashboard Cite

Staging and Functional Characterization of Pheochromocytoma and Paraganglioma by 18F-Fluorodeoxyglucose (18F-FDG) Positron Emission Tomography

Abstract: Compared with (123)I-MIBG SPECT and CT/MRI, both considered gold standards for PPGL imaging, metastases were better detected by (18)F-FDG PET. (18)F-FDG PET provides a high specificity in patients with a biochemically established diagnosis of PPGL.

Cited by 245 publications

References 29 publications

Functional Imaging Signature of Patients Presenting with Polycythemia/Paraganglioma Syndromes

Functional Imaging Signature of Patients Presenting with Polycythemia/Paraganglioma Syndromes

Semiquantitative ¹²³I-Metaiodobenzylguanidine Scintigraphy to Distinguish Pheochromocytoma and Paraganglioma from Physiologic Adrenal Uptake and Its Correlation with Genotype-Dependent Expression of Catecholamine Transporters

False Positive or False Negative PET Scan?

Contact Info

Product

Resources

About

Staging and Functional Characterization of Pheochromocytoma and Paraganglioma by 18F-Fluorodeoxyglucose (18F-FDG) Positron Emission Tomography

Abstract: Compared with (123)I-MIBG SPECT and CT/MRI, both considered gold standards for PPGL imaging, metastases were better detected by (18)F-FDG PET. (18)F-FDG PET provides a high specificity in patients with a biochemically established diagnosis of PPGL.

Cited by 245 publications

References 29 publications

Functional Imaging Signature of Patients Presenting with Polycythemia/Paraganglioma Syndromes

Functional Imaging Signature of Patients Presenting with Polycythemia/Paraganglioma Syndromes

Semiquantitative 123I-Metaiodobenzylguanidine Scintigraphy to Distinguish Pheochromocytoma and Paraganglioma from Physiologic Adrenal Uptake and Its Correlation with Genotype-Dependent Expression of Catecholamine Transporters

False Positive or False Negative PET Scan?

Contact Info

Product

Resources

About

Semiquantitative ¹²³I-Metaiodobenzylguanidine Scintigraphy to Distinguish Pheochromocytoma and Paraganglioma from Physiologic Adrenal Uptake and Its Correlation with Genotype-Dependent Expression of Catecholamine Transporters