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Horm Metab Res 2012; 44(05): 367-372
DOI: 10.1055/s-0031-1299712
Review
© Georg Thieme Verlag KG Stuttgart · New York

Current and Future Anatomical and Functional Imaging Approaches to Pheochromocytoma and Paraganglioma

H.J.L. M. Timmers
1   Department of Endocrinology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
,
D. Taieb
2   Department of Nuclear Medicine, La Timone University Hospital, Aix-Marseille University, Marseille, France
,
K. Pacak
3   Program in Reproductive and Adult Endocrinology, Eunice Kennedy Shriver National Institutes of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA
› Author Affiliations
Further Information

Publication History

received 14 October 2011

accepted 07 December 2011

Publication Date:
07 March 2012 (online)

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Abstract

After establishing a biochemical diagnosis, pheochromocytomas and extra-adrenal paragangliomas (PPGLs) can be localized using different anatomical and functional imaging modalities. These include computed tomography, magnetic resonance imaging, single-photon emission computed tomography (SPECT) using 123I-metaiodobenzylguanidine or 111In-DTPA-pentetreotide, and positron emission tomography (PET) using 6-[18F]-fluorodopamine (18F-FDA), 6-[18F]-fluoro-l-3,4-dihydroxyphenylalanine (18F-DOPA), and 2-[18F]-fluoro-2-deoxy-d-glucose. We review the currently available data on the performance of anatomical imaging, SPECT, and PET for the detection of (metastatic) PPGL as well as parasympathetic head and neck paragangliomas. We show that there appears to be no ‘gold-standard’ imaging technique for all patients with (suspected) PPGL. A tailor-made approach is warranted, guided by clinical, biochemical, and genetic characteristics. In the current era of a growing number of PET tracers, PPGL imaging has moved beyond tumor localization towards functional characterization of tumors.

Key words

FDG PET - MIBG scintigraphy - FDOPA PET - FDA PET
 

  • References

  • 1 Lenders JW, Eisenhofer G, Mannelli M, Pacak K. Phaeochromocytoma. Lancet 2005; 366: 665-675
    CrossrefPubMedGoogle Scholar
  • 2 Timmers HJ, Gimenez-Roqueplo AP, Mannelli M, Pacak K. Clinical aspects of SDHx-related pheochromocytoma and paraganglioma. Endocr Relat Cancer 2009; 16: 391-400
    CrossrefPubMedGoogle Scholar
  • 3 Timmers HJ, Kozupa A, Eisenhofer G, Raygada M, Adams KT, Solis D, Lenders JW, Pacak K. Clinical presentations, biochemical phenotypes, and genotype-phenotype correlations in patients with succinate dehydrogenase subunit B-associated pheochromocytomas and paragangliomas. J Clin Endocrinol Metab 2007; 92: 779-786
    CrossrefPubMedGoogle Scholar
  • 4 Mannelli M, Castellano M, Schiavi F, Filetti S, Giacche M, Mori L, Pignataro V, Bernini G, Giache V, Bacca A, Biondi B, Corona G, Di Trapani G, Grossrubatscher E, Reimondo G, Arnaldi G, Giacchetti G, Veglio F, Loli P, Colao A, Ambrosio MR, Terzolo M, Letizia C, Ercolino T, Opocher G. Clinically guided genetic screening in a large cohort of italian patients with pheochromocytomas and/or functional or nonfunctional paragangliomas. J Clin Endocrinol Metab 2009; 94: 1541-1547
    CrossrefPubMedGoogle Scholar
  • 5 Bayley JP, Kunst HP, Cascon A, Sampietro ML, Gaal J, Korpershoek E, Hinojar-Gutierrez A, Timmers HJ, Hoefsloot LH, Hermsen MA, Suarez C, Hussain AK, Vriends AH, Hes FJ, Jansen JC, Tops CM, Corssmit EP, de Knijff P, Lenders JW, Cremers CW, Devilee P, Dinjens WN, de Krijger RR, Robledo M. SDHAF2 mutations in familial and sporadic paraganglioma and phaeochromocytoma. Lancet Oncol 2010; 11: 366-372
    CrossrefPubMedGoogle Scholar
  • 6 Qin Y, Yao L, King EE, Buddavarapu K, Lenci RE, Chocron ES, Lechleiter JD, Sass M, Aronin N, Schiavi F, Boaretto F, Opocher G, Toledo RA, Toledo SP, Stiles C, Aguiar RC, Dahia PL. Germline mutations in TMEM127 confer susceptibility to pheochromocytoma. Nature Genet 2010; 42: 229-233
    CrossrefPubMedGoogle Scholar
  • 7 Comino-Mendez I, Gracia-Aznarez FJ, Schiavi F, Landa I, Leandro-Garcia LJ, Leton R, Honrado E, Ramos-Medina R, Caronia D, Pita G, Gomez-Grana A, de Cubas AA, Inglada-Perez L, Maliszewska A, Taschin E, Bobisse S, Pica G, Loli P, Hernandez-Lavado R, Diaz JA, Gomez-Morales M, Gonzalez-Neira A, Roncador G, Rodriguez-Antona C, Benitez J, Mannelli M, Opocher G, Robledo M, Cascon A. Exome sequencing identifies MAX mutations as a cause of hereditary pheochromocytoma. Nature Genet 2011; 43: 663-667
    CrossrefPubMedGoogle Scholar
  • 8 Benn DE, Gimenez-Roqueplo AP, Reilly JR, Bertherat J, Burgess J, Byth K, Croxson M, Dahia PL, Elston M, Gimm O, Henley D, Herman P, Murday V, Niccoli-Sire P, Pasieka JL, Rohmer V, Tucker K, Jeunemaitre X, Marsh DJ, Plouin PF, Robinson BG. Clinical presentation and penetrance of pheochromocytoma/paraganglioma syndromes. J Clin Endocrinol Metab 2006; 91: 827-836
    PubMedGoogle Scholar
  • 9 Lenders JW, Pacak K, Walther MM, Linehan WM, Mannelli M, Friberg P, Keiser HR, Goldstein DS, Eisenhofer G. Biochemical diagnosis of pheochromocytoma: which test is best?. JAMA 2002; 287: 1427-1434
    CrossrefPubMedGoogle Scholar
  • 10 Ilias I, Shulkin B, Pacak K. New functional imaging modalities for chromaffin tumors, neuroblastomas and ganglioneuromas. Trends Endocrinol Metab 2005; 16: 66-72
    CrossrefPubMedGoogle Scholar
  • 11 Shulkin BL, Wieland DM, Schwaiger M, Thompson NW, Francis IR, Haka MS, Rosenspire KC, Shapiro B, Sisson JC, Kuhl DE. PET scanning with hydroxyephedrine: an approach to the localization of pheochromocytoma. J Nucl Med 1992; 33: 1125-1131
    PubMedGoogle Scholar
  • 12 Mann GN, Link JM, Pham P, Pickett CA, Byrd DR, Kinahan PE, Krohn KA, Mankoff DA. [11C]metahydroxyephedrine and [18F]fluorodeoxyglucose positron emission tomography improve clinical decision making in suspected pheochromocytoma. Ann Surg Oncol 2006; 13: 187-197
    CrossrefPubMedGoogle Scholar
  • 13 Lynn MD, Shapiro B, Sisson JC, Beierwaltes WH, Meyers LJ, Ackerman RM, Mangner TJ. Pheochromocytoma and the normal adrenal medulla: improved visualization with I-123 MIBG scintigraphy. Radiology 1985; 155: 789-792
    PubMedGoogle Scholar
  • 14 Timmers HJ, Chen CC, Carrasquillo JA, Whatley M, Ling A, Havekes B, Eisenhofer G, Martiniova L, Adams KT, Pacak K. 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: 4757-4767
    PubMedGoogle Scholar
  • 15 Van Der Horst-Schrivers AN, Jager PL, Boezen HM, Schouten JP, Kema IP, Links TP. Iodine-123 metaiodobenzylguanidine scintigraphy in localising phaeochromocytomas – experience and meta-analysis. Anticancer Res 2006; 26: 1599-1604
    PubMedGoogle Scholar
  • 16 Taieb D, Sebag F, Hubbard JG, Mundler O, Henry JF, Conte-Devolx B. Does iodine-131 meta-iodobenzylguanidine (MIBG) scintigraphy have an impact on the management of sporadic and familial phaeochromocytoma? Clin Endocrinol (Oxf) 2004; 61: 102-108
    PubMed
  • 17 Timmers HJ, Eisenhofer G, Carrasquillo JA, Chen CC, Whatley M, Ling A, Adams KT, Pacak K. Use of 6-[18F]-fluorodopamine positron emission tomography (PET) as first-line investigation for the diagnosis and localization of non-metastatic and metastatic phaeochromocytoma (PHEO). Clin Endocrinol (Oxf) 2009; 71: 11-17
    CrossrefPubMedGoogle Scholar
  • 18 Timmers HJ, Kozupa A, Chen CC, Carrasquillo JA, Ling A, Eisenhofer G, Adams KT, Solis D, Lenders JW, Pacak K. Superiority of fluorodeoxyglucose positron emission tomography to other functional imaging techniques in the evaluation of metastatic SDHB-associated pheochromocytoma and paraganglioma. J Clin Oncol 2007; 25: 2262-2269
    CrossrefPubMedGoogle Scholar
  • 19 Loh KC, Fitzgerald PA, Matthay KK, Yeo PP, Price DC. The treatment of malignant pheochromocytoma with iodine-131 metaiodobenzylguanidine (131I-MIBG): a comprehensive review of 116 reported patients. J Endocrinol Invest 1997; 20: 648-658
    CrossrefPubMedGoogle Scholar
  • 20 Fiebrich HB, Brouwers AH, Kerstens MN, Pijl ME, Kema IP, de Jong JR, Jager PL, Elsinga PH, Dierckx RA, van der Wal JE, Sluiter WJ, de Vries EG, Links TP. 6-[F-18]Fluoro-l-dihydroxyphenylalanine positron emission tomography is superior to conventional imaging with (123)I-metaiodobenzylguanidine scintigraphy, computer tomography, and magnetic resonance imaging in localizing tumors causing catecholamine excess. J Clin Endocrinol Metab 2009; 94: 3922-3930
    CrossrefPubMedGoogle Scholar
  • 21 Hoegerle S, Nitzsche E, Altehoefer C, Ghanem N, Manz T, Brink I, Reincke M, Moser E, Neumann HP. Pheochromocytomas: detection with 18F DOPA whole body PET–initial results. Radiology 2002; 222: 507-512
    CrossrefPubMedGoogle Scholar
  • 22 Taieb D, Tessonnier L, Sebag F, Niccoli-Sire P, Morange I, Colavolpe C, De Micco C, Barlier A, Palazzo FF, Henry JF, Mundler O. The role of 18F-FDOPA and 18F-FDG-PET in the management of malignant and multifocal phaeochromocytomas. Clin Endocrinol (Oxf) 2008; 69: 580-586
    CrossrefPubMedGoogle Scholar
  • 23 Hoegerle S, Ghanem N, Altehoefer C, Schipper J, Brink I, Moser E, Neumann HP. 18F-DOPA positron emission tomography for the detection of glomus tumours. Eur J Nucl Med Mol Imaging 2003; 30: 689-694
    CrossrefPubMedGoogle Scholar
  • 24 Charrier N, Deveze A, Fakhry N, Sebag F, Morange I, Gaborit B, Barlier A, Carmona E, De Micco C, Garcia S, Mancini J, Palazzo FF, Lavieille J, Zanaret M, Henry JF, Mundler O, Taieb D. Comparison of [111In]pentetreotide-SPECT and [18F]FDOPA-PET in the localization of extra-adrenal paragangliomas: The case for a patient-tailored use of nuclear imaging modalities. Clin Endocrinol (Oxf) 2011; 74: 21-29
    CrossrefPubMedGoogle Scholar
  • 25 King KS, Chen CC, Alexopoulos DK, Whatley MA, Reynolds JC, Patronas N, Ling A, Adams KT, Xekouki P, Lando H, Stratakis CA, Pacak K. Functional Imaging of SDHx-Related Head and Neck Paragangliomas: Comparison of 18F-Fluorodihydroxyphenylalanine, 18F-Fluorodopamine, 18F-Fluoro-2-Deoxy-D-Glucose PET, 123I-Metaiodobenzylguanidine Scintigraphy, and 111In-Pentetreotide Scintigraphy. J Clin Endocrinol Metab 2011; 96: 2779-2785
    CrossrefPubMedGoogle Scholar
  • 26 Timmers HJ, Hadi M, Carrasquillo JA, Chen CC, Martiniova L, Whatley M, Ling A, Eisenhofer G, Adams KT, Pacak K. The effects of carbidopa on uptake of 6-18F-Fluoro-L-DOPA in PET of pheochromocytoma and extraadrenal abdominal paraganglioma. J Nucl Med 2007; 48: 1599-1606
    CrossrefPubMedGoogle Scholar
  • 27 Pacak K, Palkovits M. Stressor specificity of central neuroendocrine responses: implications for stress-related disorders. Endocr Rev 2001; 22: 502-548
    CrossrefPubMedGoogle Scholar
  • 28 Timmers HJ, Carrasquillo JA, Whatley M, Eisenhofer G, Chen CC, Ling A, Linehan WM, Pinto PA, Adams KT, Pacak K. Usefulness of standardized uptake values for distinguishing adrenal glands with pheochromocytoma from normal adrenal glands by use of 6-18F-fluorodopamine PET. J Nucl Med 2007; 48: 1940-1944
    CrossrefPubMedGoogle Scholar
  • 29 Ilias I, Chen CC, Carrasquillo JA, Whatley M, Ling A, Lazurova I, Adams KT, Perera S, Pacak K. Comparison of 6-18F-fluorodopamine PET with 123I-metaiodobenzylguanidine and 111in-pentetreotide scintigraphy in localization of nonmetastatic and metastatic pheochromocytoma. J Nucl Med 2008; 49: 1613-1619
    CrossrefPubMedGoogle Scholar
  • 30 Kaltsas GA, Mukherjee JJ, Grossman AB. The value of radiolabelled MIBG and octreotide in the diagnosis and management of neuroendocrine tumours. Ann Oncol 2001; 12 (Suppl. 02) S47-S50
    CrossrefPubMedGoogle Scholar
  • 31 van der Harst E, de Herder WW, Bruining HA, Bonjer HJ, de Krijger RR, Lamberts SW, van de Meiracker AH, Boomsma F, Stijnen T, Krenning EP, Bosman FT, Kwekkeboom DJ. [(123)I]metaiodobenzylguanidine and [(111)In]octreotide uptake in begnign and malignant pheochromocytomas. J Clin Endocrinol Metab 2001; 86: 685-693
    CrossrefPubMedGoogle Scholar
  • 32 Bustillo A, Telischi F, Weed D, Civantos F, Angeli S, Serafini A, Whiteman M. Octreotide scintigraphy in the head and neck. Laryngoscope 2004; 114: 434-440
    CrossrefPubMedGoogle Scholar
  • 33 Duet M, Sauvaget E, Petelle B, Rizzo N, Guichard JP, Wassef M, Le Cloirec J, Herman P, Tran Ba Huy P. Clinical impact of somatostatin receptor scintigraphy in the management of paragangliomas of the head and neck. J Nucl Med 2003; 44: 1767-1774
    PubMedGoogle Scholar
  • 34 Koopmans KP, Jager PL, Kema IP, Kerstens MN, Albers F, Dullaart RP. 111In-octreotide is superior to 123I-metaiodobenzylguanidine for scintigraphic detection of head and neck paragangliomas. J Nucl Med 2008; 49: 1232-1237
    CrossrefPubMedGoogle Scholar
  • 35 Muros MA, Llamas-Elvira JM, Rodriguez A, Ramirez A, Gomez M, Arraez MA, Valencia E, Vilchez R. 111In-pentetreotide scintigraphy is superior to 123I-MIBG scintigraphy in the diagnosis and location of chemodectoma. Nucl Med Commun 1998; 19: 735-742
    CrossrefPubMedGoogle Scholar
  • 36 Schmidt M, Fischer E, Dietlein M, Michel O, Weber K, Moka D, Stennert E, Schicha H. Clinical value of somatostatin receptor imaging in patients with suspected head and neck paragangliomas. Eur J Nucl Med Mol Imaging 2002; 29: 1571-1580
    CrossrefPubMedGoogle Scholar
  • 37 Telischi FF, Bustillo A, Whiteman ML, Serafini AN, Reisberg MJ, Gomez-Marin O, Civantos FJ, Balkany TJ. Octreotide scintigraphy for the detection of paragangliomas. Otolaryngol Head Neck Surg 2000; 122: 358-362
    CrossrefPubMedGoogle Scholar
  • 38 Huynh TT, Pacak K, Brouwers FM, Abu-Asab MS, Worrell RA, Walther MM, Elkahloun AG, Goldstein DS, Cleary S, Eisenhofer G. Different expression of catecholamine transporters in phaeochromocytomas from patients with von Hippel-Lindau syndrome and multiple endocrine neoplasia type 2. Eur J Endocrinol 2005; 153: 551-563
    CrossrefPubMedGoogle Scholar
  • 39 Kaji P, Carrasquillo JA, Linehan WM, Chen CC, Eisenhofer G, Pinto PA, Lai EW, Pacak K. The role of 6-[18F]fluorodopamine positron emission tomography in the localization of adrenal pheochromocytoma associated with von Hippel-Lindau syndrome. Eur J Endocrinol 2007; 156: 483-487
    CrossrefPubMedGoogle Scholar
  • 40 Taieb D, Sebag F, Barlier A, Tessonnier L, Palazzo FF, Morange I, Niccoli-Sire P, Fakhry N, De Micco C, Cammilleri S, Enjalbert A, Henry JF, Mundler O. . 18F-FDG avidity of pheochromocytomas and paragangliomas: a new molecular imaging signature?. J Nucl Med 2009; 50: 711-717
    CrossrefPubMed
  • 41 Timmers HJ, Kozupa K, Chen CC, Carrasquillo JA, Ling A, Eisenhofer G, Adams KT, Solis D, Lenders JW, Pacak K. Superiority of fluorodeoxyglucose positron emission tomography to other functional imaging techniques in the evaluation of metastatic SDHB-associated pheochromocytoma and paraganglioma. J Clin Oncol 2007; 26: 2262-2269
    PubMedGoogle Scholar
  • 42 Gimenez-Roqueplo AP, Favier J, Rustin P, Rieubland C, Kerlan V, Plouin PF, Rotig A, Jeunemaitre X. Functional consequences of a SDHB gene mutation in an apparently sporadic pheochromocytoma. J Clin Endocrinol Metab 2002; 87: 4771-4774
    CrossrefPubMedGoogle Scholar
  • 43 Warburg O. On the origin of cancer cells. Science 1956; 123: 309-314
    CrossrefPubMedGoogle Scholar
  • 44 Battle MR, Goggi JL, Allen L, Barnett J, Morrison MS. Monitoring tumor response to antiangiogenic sunitinib therapy with 18F-fluciclatide, an 18F-labeled alphaVbeta3-integrin and alphaV beta5-integrin imaging agent. J Nucl Med 2011; 52: 424-430
    CrossrefPubMedGoogle Scholar
  • 45 Blankenberg FG. In vivo detection of apoptosis. J Nucl Med 2008; 49 (Suppl. 02) 81S-95S
    CrossrefPubMedGoogle Scholar
  • 46 Hendrickson K, Phillips M, Smith W, Peterson L, Krohn K, Rajendran J. Hypoxia imaging with [F-18] FMISO-PET in head and neck cancer: Potential for guiding intensity modulated radiation therapy in overcoming hypoxia-induced treatment resistance. Radiother Oncol 2011; 101: 369-375
    CrossrefPubMedGoogle Scholar