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Molecular imaging and theranostic approaches in pheochromocytoma and paraganglioma

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Abstract

Pheochromocytomas and their extra-adrenal counterpart paragangliomas (PGLs; together called PPGLs), belong to the family of neural crest-derived tumors. Given the overexpression of a wide variety of specific targets in PPGLs, it seems that these tumors are optimally suited to be imaged by specific radiopharmaceuticals. Thus, theranostics approaches with somatostatin agonists and antagonists are rapidly evolving in the setting of these tumors and may be considered as the next step in the therapeutic arsenal of metastatic PPGLs.

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References

  • Archier A, Varoquaux A, Garrigue P, Montava M, Guerin C, Gabriel S, Beschmout E, Morange I, Fakhry N, Castinetti F, Sebag F, Barlier A, Loundou A, Guillet B, Pacak K, Taieb D (2015) Prospective comparison of Ga-DOTATATE and F-FDOPA PET/CT in patients with various pheochromocytomas and paragangliomas with emphasis on sporadic cases. Eur J Nucl Med Molec Imaging 43:1248–1257

  • Blake MA, Kalra MK, Maher MM, Sahani DV, Sweeney AT, Mueller PR, Hahn PF, Boland GW (2004) Pheochromocytoma: an imaging chameleon. Radiographics 24(Suppl 1):S87–S99

    Article  PubMed  Google Scholar 

  • 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 (2009) 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 94:3922–3930

    Article  CAS  PubMed  Google Scholar 

  • Fonte JS, Robles JF, Chen CC, Reynolds J, Whatley M, Ling A, Mercado-Asis LB, Adams KT, Martucci V, Fojo T, Pacak K (2012) False-negative 123I-MIBG SPECT is most commonly found in SDHB-related pheochromocytoma or paraganglioma with high frequency to develop metastatic disease. Endocr Relat Cancer 19:83–93

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Garrigue P, Bodin-Hullin A, Balasse L, Fernandez S, Essamet W, Dignat-George F, Pacak K, Guillet B, Taieb D (2017) The evolving role of succinate in tumor metabolism: an 18F–FDG-based study. J Nucl Med 58:1749–1755

  • Gonias S, Goldsby R, Matthay KK, Hawkins R, Price D, Huberty J, Damon L, Linker C, Sznewajs A, Shiboski S, Fitzgerald P (2009) Phase II study of high-dose [131I]metaiodobenzylguanidine therapy for patients with metastatic pheochromocytoma and paraganglioma. J Clin Oncol 27:4162–4168

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hartung-Knemeyer V, Rosenbaum-Krumme S, Buchbender C, Poppel T, Brandau W, Jentzen W, Antoch G, Forsting M, Bockisch A, Kuhl H (2012) Malignant pheochromocytoma imaging with [124I]mIBG PET/MR. J Clin Endocrinol Metab 97:3833–3834

    Article  CAS  PubMed  Google Scholar 

  • Hoegerle S, Nitzsche E, Altehoefer C, Ghanem N, Manz T, Brink I, Reincke M, Moser E, Neumann HP (2002) Pheochromocytomas: detection with 18F DOPA whole body PET--initial results. Radiology 222:507–512

    Article  PubMed  Google Scholar 

  • Hofman MS, Hicks RJ (2015) Moving beyond “Lumpology”: PET/CT imaging of Pheochromocytoma and Paraganglioma. Clin Canc Res 21:3815–3817

    Article  CAS  Google Scholar 

  • Hofman MS, Lau WF, Hicks RJ (2015) Somatostatin receptor imaging with 68Ga DOTATATE PET/CT: clinical utility, normal patterns, pearls, and pitfalls in interpretation. Radiographics 35:500–516

    Article  PubMed  Google Scholar 

  • Ilias I, Chen CC, Carrasquillo JA, Whatley M, Ling A, Lazurova I, Adams KT, Perera S, Pacak K (2008) Comparison of 6-18F-fluorodopamine PET with 123I-metaiodobenzylguanidine and 111in-pentetreotide scintigraphy in localization of nonmetastatic and metastatic pheochromocytoma. J Nucl Med 49:1613–1619

    Article  PubMed  PubMed Central  Google Scholar 

  • Jafri M, Whitworth J, Rattenberry E, Vialard L, Kilby G, Kumar AV, Izatt L, Lalloo F, Brennan P, Cook J, Morrison PJ, Canham N, Armstrong R, Brewer C, Tomkins S, Donaldson A, Barwell J, Cole TR, Atkinson AB, Aylwin S, Ball SG, Srirangalingam U, Chew SL, Evans DG, Hodgson SV, Irving R, Woodward E, Macdonald F, Maher ER (2013) Evaluation of SDHB, SDHD and VHL gene susceptibility testing in the assessment of individuals with non-syndromic phaeochromocytoma, paraganglioma and head and neck paraganglioma. Clin Endocrinol 78:898–906

    Article  CAS  Google Scholar 

  • Janssen I, Blanchet EM, Adams K, Chen CC, Millo CM, Herscovitch P, Taieb D, Kebebew E, Lehnert H, Fojo AT, Pacak K (2015a) Superiority of [68Ga]-DOTATATE PET/CT to other functional imaging modalities in the localization of SDHB-associated metastatic Pheochromocytoma and Paraganglioma. Clin Canc Res 21:3888–3895

    Article  CAS  Google Scholar 

  • Janssen I, Chen CC, Taieb D, Patronas NJ, Millo CM, Adams KT, Nambuba J, Herscovitch P, Sadowski SM, Fojo AT, Buchmann I, Kebebew E, Pacak K (2015b) 68Ga-DOTATATE PET/CT in the localization of head and neck paragangliomas compared to other functional imaging modalities and CT/MRI. J Nucl Med 57:186–191

  • Kaji P, Carrasquillo JA, Linehan WM, Chen CC, Eisenhofer G, Pinto PA, Lai EW, Pacak K (2007) The role of 6-[18F]fluorodopamine positron emission tomography in the localization of adrenal pheochromocytoma associated with von Hippel-Lindau syndrome. Eur J Endocrinol 156:483–487

    Article  CAS  PubMed  Google Scholar 

  • Kong G, Grozinsky-Glasberg S, Hofman MS, Callahan J, Meirovitz A, Maimon O, Pattison DA, Gross DJ, Hicks RJ (2017) Efficacy of peptide receptor radionuclide therapy for functional metastatic Paraganglioma and Pheochromocytoma. J Clin Endocrinol Metab 102:3278–3287

    Article  PubMed  Google Scholar 

  • Kroiss A, Putzer D, Frech A, Decristoforo C, Uprimny C, Gasser RW, Shulkin BL, Url C, Widmann G, Prommegger R, Sprinzl GM, Fraedrich G, Virgolini IJ (2013) A retrospective comparison between (68)Ga-DOTA-TOC PET/CT and (18)F-DOPA PET/CT in patients with extra-adrenal paraganglioma. Eur J Nucl Med Molec Imaging 40:1800–1808

    Article  CAS  Google Scholar 

  • Kroiss A, Shulkin BL, Uprimny C, Frech A, Gasser RW, Url C, Gautsch K, Madleitner R, Nilica B, Sprinzl GM, Gastl G, Fraedrich G, Virgolini IJ (2015) (68)Ga-DOTATOC PET/CT provides accurate tumour extent in patients with extraadrenal paraganglioma compared to (123)I-MIBG SPECT/CT. Eur J Nucl Med Mol Imaging 42:33–41

    Article  PubMed  Google Scholar 

  • Mantero F, Terzolo M, Arnaldi G, Osella G, Masini AM, Ali A, Giovagnetti M, Opocher G, Angeli A (2000) A survey on adrenal incidentaloma in Italy. Study Group on Adrenal Tumors Italian Society of Endocrinology. J Clin Endocrinol Metab 85:637–644

    CAS  PubMed  Google Scholar 

  • Mayo-Smith WW, Boland GW, Noto RB, Lee MJ (2001) State-of-the-art adrenal imaging. Radiographics 21:995–1012

    Article  CAS  PubMed  Google Scholar 

  • McNeil AR, Blok BH, Koelmeyer TD, Burke MP, Hilton JM (2000) Phaeochromocytomas discovered during coronial autopsies in Sydney, Melbourne and Auckland. Aust NZ J Med 30:648–652

    Article  CAS  Google Scholar 

  • Mitchell DG (1992) Chemical shift magnetic resonance imaging: applications in the abdomen and pelvis. Top Magn Reson Imaging 4:46–63

    CAS  PubMed  Google Scholar 

  • Naji M, Al-Nahhas A (2012) (68)Ga-labelled peptides in the management of neuroectodermal tumours. Eur J Nucl Med Molec Imaging 39(Suppl 1):61-67

  • Naji M, Zhao C, Welsh SJ, Meades R, Win Z, Ferrarese A, Tan T, Rubello D, Al-Nahhas A (2011) 68Ga-DOTA-TATE PET vs. 123I-MIBG in identifying malignant neural crest tumours. Mol Imaging Biol 13:769–775

    Article  PubMed  Google Scholar 

  • Neumann HP, Erlic Z, Boedeker CC, Rybicki LA, Robledo M, Hermsen M, Schiavi F, Falcioni M, Kwok P, Bauters C, Lampe K, Fischer M, Edelman E, Benn DE, Robinson BG, Wiegand S, Rasp G, Stuck BA, Hoffmann MM, Sullivan M, Sevilla MA, Weiss MM, Peczkowska M, Kubaszek A, Pigny P, Ward RL, Learoyd D, Croxson M, Zabolotny D, Yaremchuk S, Draf W, Muresan M, Lorenz RR, Knipping S, Strohm M, Dyckhoff G, Matthias C, Reisch N, Preuss SF, Esser D, Walter MA, Kaftan H, Stover T, Fottner C, Gorgulla H, Malekpour M, Zarandy MM, Schipper J, Brase C, Glien A, Kuhnemund M, Koscielny S, Schwerdtfeger P, Valimaki M, Szyfter W, Finckh U, Zerres K, Cascon A, Opocher G, Ridder GJ, Januszewicz A, Suarez C, Eng C (2009) Clinical predictors for germline mutations in head and neck paraganglioma patients: cost reduction strategy in genetic diagnostic process as fall-out. Cancer Res 69:3650–3656

    Article  CAS  PubMed  Google Scholar 

  • Pandit-Taskar N, Zanzonico PB, Staton KD, Carrasquillo JA, Reidy-Lagunes D, Lyashchenko SK, Burnazi E, Zhang H, Lewis JS, Blasberg R, Larson SM, Weber WA, Modak S (2017) Biodistribution and dosimetry of (18)F-meta Fluorobenzyl guanidine (MFBG): a first-in-human PET-CT imaging study of patients with neuroendocrine malignancies. J Nucl Med 117.193169

  • Papathomas TG, Gaal J, Corssmit EP, Oudijk L, Korpershoek E, Heimdal K, Bayley JP, Morreau H, van Dooren M, Papaspyrou K, Schreiner T, Hansen T, Andresen PA, Restuccia DF, van Kessel I, van Leenders GJ, Kros JM, Looijenga LH, Hofland LJ, Mann W, van Nederveen FH, Mete O, Asa SL, de Krijger RR, Dinjens WN (2014) Non-pheochromocytoma (PCC)/paraganglioma (PGL) tumors in patients with succinate dehydrogenase-related PCC-PGL syndromes: a clinicopathological and molecular analysis. Eur J Endocrinol 170:1–12

    Article  CAS  PubMed  Google Scholar 

  • Park BK, Kim B, Ko K, Jeong SY, Kwon GY (2006) Adrenal masses falsely diagnosed as adenomas on unenhanced and delayed contrast-enhanced computed tomography: pathological correlation. Eur Radiol 16:642–647

    Article  PubMed  Google Scholar 

  • Park BK, Kim CK, Kwon GY, Kim JH (2007) Re-evaluation of pheochromocytomas on delayed contrast-enhanced CT: washout enhancement and other imaging features. Eur Radiol 17:2804–2809

    Article  PubMed  Google Scholar 

  • Pasini B, McWhinney SR, Bei T, Matyakhina L, Stergiopoulos S, Muchow M, Boikos SA, Ferrando B, Pacak K, Assie G, Baudin E, Chompret A, Ellison JW, Briere JJ, Rustin P, Gimenez-Roqueplo AP, Eng C, Carney JA, Stratakis CA (2008) Clinical and molecular genetics of patients with the Carney-Stratakis syndrome and germline mutations of the genes coding for the succinate dehydrogenase subunits SDHB, SDHC, and SDHD. Eur J Hum Genet 16:79–88

    Article  CAS  PubMed  Google Scholar 

  • Platts JK, Drew PJ, Harvey JN (1995) Death from phaeochromocytoma: lessons from a post-mortem survey. J R Coll Physicians Lond 29:299–306

    CAS  PubMed  Google Scholar 

  • Sharma P, Mukherjee A, Karunanithi S, Naswa N, Kumar R, Ammini AC, Bal C (2015) Accuracy of 68Ga DOTANOC PET/CT imaging in patients with multiple endocrine Neoplasia syndromes. Clin Nucl Med 40:e351–e356

    Article  PubMed  Google Scholar 

  • Sharma P, Thakar A, Suman Kc S, Dhull VS, Singh H, Naswa N, Reddy RM, Karunanithi S, Kumar R, Malhotra A, Bal C (2013) 68Ga-DOTANOC PET/CT for baseline evaluation of patients with head and neck Paraganglioma. J Nucl Med 54:841–847

    Article  CAS  PubMed  Google Scholar 

  • Stenstrom G, Svardsudd K (1986) Pheochromocytoma in Sweden 1958-1981. An analysis of the National Cancer Registry Data. Acta Med Scand 220:225–232

    Article  CAS  PubMed  Google Scholar 

  • Strosberg J, El-Haddad G, Wolin E, Hendifar A, Yao J, Chasen B, Mittra E, Kunz PL, Kulke MH, Jacene H, Bushnell D, O’Dorisio TM, Baum RP, Kulkarni HR, Caplin M, Lebtahi R, Hobday T, Delpassand E, Van Cutsem E, Benson A, Srirajaskanthan R, Pavel M, Mora J, Berlin J, Grande E, Reed N, Seregni E, Oberg K, Lopera Sierra M, Santoro P, Thevenet T, Erion JL, Ruszniewski P, Kwekkeboom D, Krenning E, Investigators N-T (2017) Phase 3 trial of 177Lu-Dotatate for Midgut Neuroendocrine Tumors. N Engl J Med 376:125–135

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sutton MG, Sheps SG, Lie JT (1981) Prevalence of clinically unsuspected pheochromocytoma. Review of a 50-year autopsy series. Mayo Clin Proc 56:354–360

    CAS  PubMed  Google Scholar 

  • Timmers HJ, Chen CC, Carrasquillo JA, Whatley M, Ling A, Eisenhofer G, King KS, Rao JU, Wesley RA, Adams KT, Pacak K (2012) Staging and functional characterization of pheochromocytoma and paraganglioma by 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography. J Natl Cancer Inst 104:700–708

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Timmers HJ, Chen CC, Carrasquillo JA, Whatley M, Ling A, Havekes B, Eisenhofer G, Martiniova L, Adams KT, Pacak K (2009a) 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 94:4757–4767

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Timmers HJ, Eisenhofer G, Carrasquillo JA, Chen CC, Whatley M, Ling A, Adams KT, Pacak K (2009b) 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 71:11–17

    Article  Google Scholar 

  • Varghese JC, Hahn PF, Papanicolaou N, Mayo-Smith WW, Gaa JA, Lee MJ (1997) MR differentiation of phaeochromocytoma from other adrenal lesions based on qualitative analysis of T2 relaxation times. Clin Radiol 52:603–606

    Article  CAS  PubMed  Google Scholar 

  • Zovato S, Kumanova A, Dematte S, Sansovini M, Bodei L, Di Sarra D, Casagranda E, Severi S, Ambrosetti A, Schiavi F, Opocher G, Paganelli G (2012) Peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTATATE in individuals with neck or mediastinal paraganglioma (PGL). Horm Metab Res 44:411–414

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

This research was supported, in part, by the Intramural Research Program of the NIH, Eunice Kennedy Shriver NICHD.

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Authors and Affiliations

  1. Department of Nuclear Medicine, La Timone University Hospital, CERIMED, Aix-Marseille University, 264, rue Saint-Pierre, 13385, Marseille, France

    David Taïeb

  2. Section on Medical Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA

    Karel Pacak

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Correspondence to David Taïeb.

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Taïeb, D., Pacak, K. Molecular imaging and theranostic approaches in pheochromocytoma and paraganglioma. Cell Tissue Res 372, 393–401 (2018). https://doi.org/10.1007/s00441-018-2791-4

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