Functional Imaging of Paragangliomas with an Emphasis on Von Hippel–Lindau-Associated Disease: A Mini Review

Main Article Content

Ioannis Ilias
Georgios Meristoudis

Keywords

imaging, paraganglioma, pheochromocytoma, radionuclide, von-Hippel-Lindau

Abstract

Few reports have presented data and results on functional (i.e., nuclear medicine) imaging of paragangliomas and pheochromocytomas (PGLs/PHEOs) for von Hippel–Lindau (VHL) patients. Nuclear medicine localization modalities for chromaffin tumors can be specific or nonspecific. Specific methods make use of the expression of the human norepinephrine transporter (hNET) and vesicular monoamine transporters (VMATs) by these tumors. These permit the use of radiolabeled ligands that enter the synthesis and storage pathway of catecholamines. Nonspecific methods are not related to the synthesis, uptake, or storage of catecholamines but make use of the tumors’ high glucose metabolism or expression of somatostatin receptors. Consensuses and guidelines suggest that metastatic and sporadic PHEOs/PGLs in VHL patients (as in patients with chromaffin tumors of yet unknown genotype) should be evaluated first with 18F-dihydroxyphenylalanine (18F-DOPA) positron emission tomography/computed tomography (PET/CT). The functional imaging of second choice is 123I-metaiodobenzylguanidine (123I-MIBG) for PHEOs in VHL patients. 123I-MIBG, 68Ga-DOTATATE/DOTATOC/DOTANOC PET/CT, or 18F-fluorodeoxyglucose (18F-FDG) PET/CT can be a second choice of functional imaging for PGLs in VHL patients.

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References

1. Tischler AS, Pacak K, Eisenhofer G. The adrenal medulla and extra-adrenal paraganglia: Then and now. Endocr Pathol. 2014 Mar;25(1):49–58. http://dx.doi.org/10.1007/s12022-013-9286-3
2. Loosli N, Kohler BB, Pechere-Bertschi A, Karenovics W, Triponex F. Pheochromocytome et paragangliome: Que doit retenir le praticien? Rev Med Suisse. 2014 Sep 10;10(441):1650–2, 4–5.
3. Tischler AS. Pheochromocytoma and extra-adrenal paraganglioma updates. Arch Pathol Lab Med. 2008;132(8):1272–84.
4. McNicol AM, Young WF, Kawashima A, Komminoth P, Tischler AS. Benign phaeochromocytoma. In: DeLellis RA, Lloyd RV, Heitz PU, Eng C, editors. World Health Organization classification of tumours pathology and genetics tumours of endocrine organs. 3rd ed. Lyon: World Health Organization, International Agency for Research on Cancer Press; 2004. p. 151–5.
5. 8700/0 Pheochromocytoma, NOS [database on the Internet]. World Health Organization, International Agency for Research on Cancer; 2017 [cited July 25, 2017]. Available from: https://codes.iarc.fr/code/3217.
6. 8700/0 Adrenal medullary paraganglioma [database on the Internet]. World Health Organization, International Agency for Research on Cancer; 2017 [cited July 25, 2017]. Available from: http://codes.iarc.fr/code/3218
7. 8700/3 Pheochromocytoma, malignant [database on the Internet]. World Health Organization, International Agency for Research on Cancer; 2017. Available from: http://codes.iarc.fr/code/3222
8. 8700/3 Adrenal medullary paraganglioma, malignant [database on the Internet]. World Health Organization, International Agency for Research on Cancer; 2017. Available from: http://codes.iarc.fr/code/3223
9. Ilias I, Pacak K. A clinical overview of pheochromocytomas/paragangliomas and carcinoid tumors. Nucl Med Biol. 2008 Aug;35 Suppl 1:S27–34. http://dx.doi.org/10.1016/j.nucmedbio.2008.04.007
10. Maher ER, Neumann HPH, Richard S. von Hippel–Lindau disease: A clinical and scientific review. Eur J Hum Genet. 2011;19:617–23. http://dx.doi.org/10.1038/ejhg.2010.175
11. Ashouri K, Mohseni S, Tourtelot J, Sharma P, Spiess PE. Implications of Von Hippel-Lindau syndrome and renal cell carcinoma. J Kidney Cancer VHL. 2015;2(4):163–73. http://dx.doi.org/10.15586/jkcvhl.2015.41
12. Fliedner SM, Lehnert H, Pacak K. Metastatic paraganglioma. Semin Oncol. 2010 Dec;37(6):627–37. http://dx.doi.org/10.1053/j.seminoncol.2010.10.017
13. Ilias I, Pacak K. Current approaches and recommended algorithm for the diagnostic localization of pheochromocytoma. J Clin Endocrinol Metab. 2004;89:479–91. http://dx.doi.org/10.1210/jc.2003-031091
14. Ilias I, Meristoudis G, Notopoulos A. A probabilistic assessment of the diagnosis of paraganglioma/pheochromocytoma based on clinical criteria and biochemical/imaging findings. Hell J Nucl Med. 2015 Jan–Apr;18(1):63–5.
15. 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 Jul;61(1):102–8. http://dx.doi.org/10.1111/j.1365-2265.2004.02077.x
16. Ilias I, Divgi C, Pacak K. Current role of metaiodobenzylguanidine in the diagnosis of pheochromocytoma and medullary thyroid cancer. Semin Nucl Med. 2011;41(5):364–8. http://dx.doi.org/10.1053/j.semnuclmed.2011.03.003
17. Lenders JW, Duh QY, Eisenhofer G, Gimenez-Roqueplo AP, Grebe SK, Murad MH, et al. Pheochromocytoma and paraganglioma: An endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2014 Jun;99(6):1915–42. http://dx.doi.org/10.1210/jc.2014-1498
18. Wiseman GA, Pacak K, O’Dorisio MS, Neumann DR, Waxman AD, Mankoff DA, et al. Usefulness of 123I-MIBG scintigraphy in the evaluation of patients with known or suspected primary or metastatic pheochromocytoma or paraganglioma: Results from a prospective multicenter trial. J Nucl Med. 2009 Sep;50(9):1448–54. http://dx.doi.org/10.2967/jnumed.108.058701
19. Taieb D, Imperiale A, Pacak K. (18)F-DOPA: The versatile radiopharmaceutical. Eur J Nucl Med Mol Imaging. 2016 Jun;43(6):1187–9. http://dx.doi.org/10.1007/s00259-016-3354-0
20. Archier A, Varoquaux A, Garrigue P, Montava M, Guerin C, Gabriel S, et al. Prospective comparison of (68)Ga-DOTATATE and (18)F-FDOPA PET/CT in patients with various pheochromocytomas and paragangliomas with emphasis on sporadic cases. Eur J Nucl Med Mol Imaging. 2016 Jul;43(7):1248–57. http://dx.doi.org/10.1007/s00259-015-3268-2
21. Castinetti F, Kroiss A, Kumar R, Pacak K, Taieb D. 15 Years of paraganglioma: Imaging and imaging-based treatment of pheochromocytoma and paraganglioma. Endocr Relat Cancer. 2015 Aug;22(4):T135–45. http://dx.doi.org/10.1530/ERC-15-0175
22. Taieb D, Timmers HJ, Shulkin BL, Pacak K. Renaissance of (18)F-FDG positron emission tomography in the imaging of pheochromocytoma/paraganglioma. J Clin Endocrinol Metab. 2014 Jul;99(7):2337–9. http://dx.doi.org/10.1210/jc.2014-1048
23. Timmers HJ, Kozupa A, Chen CC, Carrasquillo JA, Ling A, Eisenhofer G, et al. 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 Jun 1;25(16):2262–9. http://dx.doi.org/10.1200/JCO.2006.09.6297
24. Hofman MS, Hicks RJ. Moving beyond “Lumpology”: PET/CT imaging of pheochromocytoma and paraganglioma. Clin Cancer Res. 2015 Sep 01;21(17):3815–17. http://dx.doi.org/10.1158/1078-0432.CCR-15-1073
25. Tirosh A, Papadakis GZ, Millo C, Sadowski SM, Herscovitch P, Pacak K, et al. Association between neuroendocrine tumors biomarkers and primary tumor site and disease type based on total 68Ga-DOTATATE-Avid tumor volume measurements. Eur J Endocrinol. 2017 May;176(5):575–82. http://dx.doi.org/10.1530/EJE-16-1079
26. Janssen I, Chen CC, Millo CM, Ling A, Taieb D, Lin FI, et al. PET/CT comparing (68)Ga-DOTATATE and other radiopharmaceuticals and in comparison with CT/MRI for the localization of sporadic metastatic pheochromocytoma and paraganglioma. Eur J Nucl Med Mol Imaging. 2016 Sep;43(10):1784–91. http://dx.doi.org/10.1007/s00259-016-3357-x
27. Chen MY, Chew EY, Reynolds JC, Chao DL, Oldfield EH. Metastatic brainstem pheochromocytoma in a patient with von Hippel-Lindau disease. Case illustration. J Neurosurg. 2001 Jan;94(1):138. http://dx.doi.org/10.3171/jns.2001.94.1.0138
28. Thoren KL, Balingit AG, Billingsley J. Multiple pheochromocytomas in a patient with blurred vision. Clin Nucl Med. 2008 Sep;33(9):597–601. http://dx.doi.org/10.1097/RLU.0b013e3181813096
29. Huynh TT, Pacak K, Brouwers FM, Abu-Asab MS, Worrell RA, Walther MM, et al. Different expression of catecholamine transporters in phaeochromocytomas from patients with von Hippel-Lindau syndrome and multiple endocrine neoplasia type 2. Eur J Endocrinol. 2005 Oct;153(4):551–63. http://dx.doi.org/10.1530/eje.1.01987
30. Taieb D, Timmers HJ, Hindie E, Guillet BA, Neumann HP, Walz MK, et al. EANM 2012 guidelines for radionuclide imaging of phaeochromocytoma and paraganglioma. Eur J Nucl Med Mol Imaging. 2012 Dec;39(12):1977–95. http://dx.doi.org/10.1007/s00259-012-2215-8
31. van Berkel A, Rao JU, Lenders JW, Pellegata NS, Kusters B, Piscaer I, et al. Semiquantitative 123I-Metaiodobenzylguanidine scintigraphy to distinguish pheochromocytoma and paraganglioma from physiologic adrenal uptake and its correlation with genotype-dependent expression of catecholamine transporters. J Nucl Med. 2015 Jun;56(6):839–46. http://dx.doi.org/10.2967/jnumed.115.154815
32. Srirangalingam U, Khoo B, Walker L, MacDonald F, Skelly RH, George E, et al. Contrasting clinical manifestations of SDHB and VHL associated chromaffin tumours. Endocr Relat Cancer. 2009 Jun;16(2):515–25. http://dx.doi.org/10.1677/ERC-08-0239
33. Gabriel S, Blanchet EM, Sebag F, Chen CC, Fakhry N, Deveze A, et al. Functional characterization of nonmetastatic paraganglioma and pheochromocytoma by (18) F-FDOPA PET: Focus on missed lesions. Clin Endocrinol (Oxf). 2013 Aug;79(2):170–7. http://dx.doi.org/10.1111/cen.12126
34. 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 Dec;94(12):4757–67. http://dx.doi.org/10.1210/jc.2009-1248
35. Rischke HC, Benz MR, Wild D, Mix M, Dumont RA, Campbell D, et al. Correlation of the genotype of paragangliomas and pheochromocytomas with their metabolic phenotype on 3,4-dihydroxy-6-18F-fluoro-L-phenylalanin PET. J Nucl Med. 2012 Sep;53(9):1352–8. http://dx.doi.org/10.2967/jnumed.111.101303
36. Chondrogiannis S, Grassetto G, Marzola MC, Rampin L, Massaro A, Bellan E, et al. 18F-DOPA PET/CT biodistribution consideration in 107 consecutive patients with neuroendocrine tumours. Nucl Med Commun. 2012 Feb;33(2):179–84. http://dx.doi.org/10.1097/MNM.0b013e32834e0974
37. Kaji P, Carrasquillo JA, Linehan WM, Chen CC, Eisenhofer G, Pinto PA, et al. 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 Apr;156(4):483–7. http://dx.doi.org/10.1530/EJE-06-0712
38. Barbolosi D, Hapdey S, Battini S, Faivre C, Mancini J, Pacak K, et al. Determination of the unmetabolised (18)F-FDG fraction by using an extension of simplified kinetic analysis method: Clinical evaluation in paragangliomas. Med Biol Eng Comput. 2016 Jan;54(1):103–11. http://dx.doi.org/10.1007/s11517-015-1318-3
39. Martucci VL, Lorenzo ZG, Weintraub M, del Rivero J, Ling A, Merino M, et al. Association of urinary bladder paragangliomas with germline mutations in the SDHB and VHL genes. Urol Oncol. 2015 Apr;33(4):167 e13–20.
40. Weisbrod AB, Kitano M, Gesuwan K, Millo C, Herscovitch P, Nilubol N, et al. Clinical utility of functional imaging with (1)(8)F-FDOPA in Von Hippel-Lindau syndrome. J Clin Endocrinol Metab. 2012 Apr;97(4):E613–17. http://dx.doi.org/10.1210/jc.2011-2626
41. Taieb D, Varoquaux A, Chen CC, Pacak K. Current and future trends in the anatomical and functional imaging of head and neck paragangliomas. Semin Nucl Med. 2013 Nov;43(6):462–73. http://dx.doi.org/10.1053/j.semnuclmed.2013.06.005
42. Mukherjee A, Karunanithi S, Bal C, Kumar R. 68Ga DOTANOC PET/CT aiding in the diagnosis of von Hippel-Lindau syndrome by detecting cerebellar hemangioblastoma and adrenal pheochromocytoma. Clin Nucl Med. 2014 Oct;39(10):920–1. http://dx.doi.org/10.1097/RLU.0000000000000486
43. Ambrosini V, Campana D, Allegri V, Opocher G, Fanti S. 68Ga-DOTA-NOC PET/CT detects somatostatin receptors expression in von hippel-lindau cerebellar disease. Clin Nucl Med. 2011 Jan;36(1):64–5. http://dx.doi.org/10.1097/RLU.0b013e3181fef14a
44. Dalm SU, Haeck J, Doeswijk GN, de Blois E, de Jong M, van Deurzen C. SSTR-mediated breast cancer imaging: Is there a role for radiolabeled SSTR antagonists? J Nucl Med. 2017 Apr 27; [Epub ahead of print]. http://dx.doi.org/10.2967/jnumed.116.189035
45. Wadas TJ, Eiblmaier M, Zheleznyak A, Sherman CD, Ferdani R, Liang K, et al. Preparation and biological evaluation of 64Cu-CB-TE2A-sst2-ANT, a somatostatin antagonist for PET imaging of somatostatin receptor-positive tumors. J Nucl Med. 2008 Nov;49(11):1819–27. http://dx.doi.org/10.2967/jnumed.108.054502
46. Opalinska M, Hubalewska-Dydejczyk A, Sowa-Staszczak A. Radiolabeled peptides: Current and new perspectives. Q J Nucl Med Mol Imaging. 2017 Jun;61(2):153–67.
47. Opalinska M, Hubalewska-Dydejczyk A, Sowa-Staszczak A, Stefanska A. NEN – The role of somatostatin receptor scintigraphy in clinical setting. Nucl Med Rev Cent East Eur. 2016;19(2):118–25. http://dx.doi.org/10.5603/NMR.2016.0023
48. Wang X, Fani M, Schulz S, Rivier J, Reubi JC, Maecke HR. Comprehensive evaluation of a somatostatin-based radiolabelled antagonist for diagnostic imaging and radionuclide therapy. Eur J Nucl Med Mol Imaging. 2012 Dec;39(12):1876–85. http://dx.doi.org/10.1007/s00259-012-2231-8
49. Vortmeyer AO, Alomari AK. Pathology of the nervous system in Von Hippel-Lindau disease. J Kidney Cancer VHL. 2015;2(3):114–29. http://dx.doi.org/10.15586/jkcvhl.2015.35
50. Oosting SF, van Asselt SJ, Brouwers AH, Bongaerts AH, Steinberg JD, de Jong JR, et al. 89Zr-Bevacizumab PET visualizes disease manifestations in patients with von Hippel-Lindau disease. J Nucl Med. 2016 Aug;57(8):1244–50. http://dx.doi.org/10.2967/jnumed.115.167643
51. Taieb D, Hicks RJ, Pacak K. Radiopharmaceuticals in paraganglioma imaging: Too many members on board? Eur J Nucl Med Mol Imaging. 2016 Mar;43(3):391–3. http://dx.doi.org/10.1007/s00259-015-3213-4
52. Bozkurt MF, Virgolini I, Balogova S, Beheshti M, Rubello D, Decristoforo C, et al. Guideline for PET/CT imaging of neuroendocrine neoplasms with 68Ga-DOTA-conjugated somatostatin receptor targeting peptides and 18F-DOPA. Eur J Nucl Med Mol Imaging. 2017 May 25;44(9):1588–601. http://dx.doi.org/10.1007/s00259-017-3728-y