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Hormones

, Volume 12, Issue 1, pp 58–68 | Cite as

The evolution in the use of MIBG scintigraphy in pheochromocytomas and paragangliomas

  • Vittoria Rufini
  • Giorgio Treglia
  • Germano Perotti
  • Alessandro Giordano
Review

Abstract

Radioiodinated metaiodobenzylguanidine (MIBG) was developed in the late 1970’s, at the Michigan University Medical center, for imaging of the adrenal medulla and its diseases. Soon after, MIBG was shown to depict a wide range of tumors of neural crest origin other than pheochromocytomas/paragangliomas (Pheo/PGL) with the result that its use rapidly spread to many countries. After more than 30 years of clinical application, MIBG continues to be the most widespread radiopharmaceutical for the functional imaging of Pheo/PGL in spite of the emergent role of PET agents for detection of these tumors. In this paper we review the evolution in the use of MIBG over more than 30 years of experimental and clinical applications, with particular focus on the uptake mechanisms, pharmacokinetics, biodistribution and drug interaction as well as on clinical studies in Pheo/PGL also in comparison to other gamma-emitters tracers and PET radiopharmaceuticals.

Key words

Metaiodobenzylguanidine Nuclear medicine Paraganglioma Pheochromocytoma 

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References

  1. 1.
    Wieland DM, Wu JL, Brown LE, Mangner TJ, Swanson DP, Beierwaltes WH, 1980 Radiolabeled adrenergic neuron blocking agents: adrenomedullary imaging with 131I-iodobenzylguanidine. J Nucl Med 21: 349–353.PubMedGoogle Scholar
  2. 2.
    Sisson JC, Frager Ms, Valk TW, et al, 1981 Scintigraphic localization of pheochromocytoma. N Engl J Med 305: 12–17.CrossRefGoogle Scholar
  3. 3.
    Geatti O, Shapiro B, Sisson JC, et al, 1985 Iodine-131 metaiodobenzylguanidine scintigraphy for the location of neuroblastoma: preliminary experience in ten cases. J Nucl Med 26: 736–742.PubMedGoogle Scholar
  4. 4.
    Von Moll L, McEwan AJ, Shapiro B, et al, 1987 Iodine-131 MIBG scintigraphy of neuroendocrine tumors other than pheochromocytoma and neuroblastoma. J Nucl Med 28: 979–988.Google Scholar
  5. 5.
    Sisson JC, Shapiro B, Beierwaltes WH, et al, 1984 Radiopharmaceutical treatment of malignant pheochromocytoma. J Nucl Med 25: 197–206.PubMedGoogle Scholar
  6. 6.
    McEwan AJ, Shapiro B, Sisson JC, et al, 1985 Radioiodobenzylguanidine for the scintigraphic location and therapy of adrenergic tumors. Semin Nucl Med 5: 132–153.CrossRefGoogle Scholar
  7. 7.
    Sisson JC, Shapiro B, Meyers L, et al, 1987 Metaiodobenzylguanidine to map scintigraphically the adrenergic nervous system in man. J Nucl Med 28: 1625–1636.PubMedGoogle Scholar
  8. 8.
    Agostini D, Verberne HJ, Hamon, Manrique A, 2008 Cardiac 123I-mIBG scintigraphy in heart failure. Q J Nucl Med Mol Imaging 52: 369–377.PubMedGoogle Scholar
  9. 9.
    Eisenhofer G, Pacak K, Goldstein DS, Chen C, Shulkin B, 2000 123I-MIBG scintigraphy of catecholamine systems: impediments to applications in clinical medicine [letter]. Eur J Nucl Med 27: 611–612.PubMedGoogle Scholar
  10. 10.
    Rufini V, Shulkin B, 2008 The evolution in the use of MIBG in more than 25 years of experimental and clinical applications. Q J Nucl Med Mol Imaging 52: 341–350.PubMedGoogle Scholar
  11. 11.
    Vaidyanathan G, 2008 Meta-iodobenzylguanidine and analogues: chemistry and biology. Q J Nucl Med Mol Imaging 52: 351–368.PubMedGoogle Scholar
  12. 12.
    Vallabhajosula S, Nikolopoulou A, 2011 Radioiodinated metaiodobenzylguanidine (MIBG): radiochemistry, biology, and pharmacology. Semin Nucl Med 41: 324–333.CrossRefGoogle Scholar
  13. 13.
    Wafelman AR, Hoefnagel CA, Maes RA, Beijnen JH, 1994 Radioiodinated metaiodobenzylguanidine: a review of its biodistribution and pharmacokinetics, drug interaction, cytotoxicity and dosimetry. Eur J Nucl Med 21: 545–559.CrossRefGoogle Scholar
  14. 14.
    Bombardieri E, Giammarile F, Aktolun C, et al, 2010 European Association for Nuclear Medicine. 131I/123I-metaiodobenzylguanidine (mIBG) scintigraphy: procedure guidelines for tumour imaging. Eur J Nucl Med Mol Imaging 37: 2436–2446.CrossRefGoogle Scholar
  15. 15.
    ICRP Publication 80, 1998 Radiation dose to patients from radiopharmaceuticals. Annals of ICRP. Oxford, Pergamon Press.Google Scholar
  16. 16.
    Shulkin BL, Shapiro B, Francis IR, Dorr R, Shen SW, Sisson JC, 1986 Primary extra-adrenal pheochromocytoma: positive I-123 MIBG imaging with negative I-131 MIBG imaging. Clin Nucl Med 11: 851–854.CrossRefGoogle Scholar
  17. 17.
    Barrett JA, Joyal JL, Hillier SM, et al, 2010 Comparison of high-specific-activity ultratrace 123/131I-MIBG and carrier-added 123/131I-MIBG on efficacy, pharmacokinetics, and tissue distribution. Cancer Biother Radiopharm 25: 299–308.CrossRefGoogle Scholar
  18. 18.
    Matthay KK, Weiss B, Villablanca JG, et al, 2012 Dose escalation study of no-carrier-added 131I-metaiodobenzylguanidine for relapsed or refractory neuroblastoma: new approaches to neuroblastoma therapy consortium trial. J Nucl Med 53: 1155–1163.CrossRefGoogle Scholar
  19. 19.
    Watanabe S, Hanaoka H, Liang JX, Iida Y, Endo K, Ishioka NS, 2010 PET imaging of norepinephrine transporter-expressing tumors using 76Br-meta-bromobenzylguanidine. J Nucl Med 51: 1472–1479.CrossRefGoogle Scholar
  20. 20.
    Rozovsky K, Koplewitz BZ, Krausz Y, et al, 2008 Added value of SPECT/CT for correlation of MIBG scintigraphy and diagnostic CT in neuroblastoma and pheochromocytoma. AJR Am J Roentgenol 190: 1085–1090.CrossRefGoogle Scholar
  21. 21.
    Meyer-Rochow GY, Schembri GP, Benn DE, et al, 2010 The utility of metaiodobenzylguanidine single photon emission computed tomography/computed tomography (MIBG SPECT/CT) for the diagnosis of pheochromocytoma. Ann Surg Oncol 17: 392–400.CrossRefGoogle Scholar
  22. 22.
    Taïeb D, Timmers HJ, Hindié E, et al, 2012 EANM 2012 guidelines for radionuclide imaging of phaeochromocytoma and paraganglioma. Eur J Nucl Med Mol Imaging 39: 1977–1995.CrossRefGoogle Scholar
  23. 23.
    Khafagi FA, Shapiro B, Fig LM, Mallette S, Sisson JC, 1989 Labetalol reduces iodine-131-MIBG uptake by pheochromocytoma and normal tissues. J Nucl Med 30: 481–489.PubMedGoogle Scholar
  24. 24.
    Solanki KK, Bomanji J, Moyes J, Mather SJ, Trainer PJ, Britton KE, 1992 A pharmacological guide to medicines which interfere with the biodistribution of radiolabelled meta-iodobenzylguanidine (MIBG). Nucl Med Commun 13: 513–521.CrossRefGoogle Scholar
  25. 25.
    Blake GM, Lewington VJ, Fleming JS, Zivanovic MA, Ackery DM, 1988 Modification by nifedipine of 131I-meta-iodobenzylguanidine kinetics in malignant phaeochromocytoma. Eur J Nucl Med 14: 345–348.PubMedGoogle Scholar
  26. 26.
    Martiniova L, Perera SM, Brouwers FM, et al, 2011 Increased uptake of [123I]meta-iodobenzylguanidine, [18F]fluorodopamine and [3H]norepinephrine in mouse pheochromocytoma cells and tumors after treatment with the histone deacetylase inhibitors. Endocr Related Cancer 18: 143–157.CrossRefGoogle Scholar
  27. 27.
    Okuyama C, Ushjima Y, Kubota T, et al, 2003 123I-metaiodobenzylguanidine uptake in the nape of the neck of children: likely visualization of brown adipose tissue. J Nucl Med 44: 1421–1425.PubMedGoogle Scholar
  28. 28.
    Gelfand MJ, 2004 123I-MIBG uptake in the neck and shoulders of a neuroblastoma patient: damage to sympathetic innervation blocks uptake in brown adipose tissue. Pediatr Radiol 34: 577–579.CrossRefGoogle Scholar
  29. 29.
    Hadi M, Chen CC, Whatley M, Pacak K, Carrasquillo JA, 2007 Brown fat imaging with (18)F-6-fluorodopamine PET/CT, (18)F-FDG PET/CT, and (123)I-MIBG SPECT: a study of patients being evaluated for pheochromocytoma. J Nucl Med 48: 1077–1083.CrossRefGoogle Scholar
  30. 30.
    Ilias I, Divgi C, Pacak H, 2011 Current role of metaiodobenzylguanidine in the diagnosis of pheochromocytoma and medullary thyroid cancer. Semin Nucl Med 41: 364–368.CrossRefGoogle Scholar
  31. 31.
    Havekes B, Lai EW, Corssmit PM, Romijn JA, Timmers HJLM, Pacak K, 2008 Detection and treatment of pheochromocytomas and paragangliomas: current standing of MIBG scintigraphy and future role of PET imaging. Q J Nucl Med Mol Imaging 52: 419–429.PubMedGoogle Scholar
  32. 32.
    Boersma HH, Wensing JW, Kho TL, de Brauw LM, Liem IH, van Kroonenburgh MJ, 2000 Transient enhance uptake of 123I-metaiodobenzylguanidine in the contralateral adrenal region after resection of an adrenal pheochromocytoma. N Engl J Med 342: 1450–1451.CrossRefGoogle Scholar
  33. 33.
    Cecchin D, Lumachi F, Marzola MC, et al, 2006 A meta-iodobenzylguanidine scintigraphic scoring system increases accuracy in the diagnostic management of pheochromocytoma. Endocr Relat Cancer 13: 525–533.CrossRefGoogle Scholar
  34. 34.
    Shapiro B, Copp JE, Sisson JC, Eyre PL, Wallis J, Beierwaltes WH, 1985 131-Iodine-metaiodobenzylguanidine for the locating of suspected pheochromocytoma: experience in 400 cases. J Nucl Med 26: 576–585.PubMedGoogle Scholar
  35. 35.
    Rufini V, Calcagni ML, Baum RP, 2006 Imaging of neuroendocrine tumors. Semin Nucl Med 36: 228–247.CrossRefGoogle Scholar
  36. 36.
    Taïeb D, Sebag F, Hubbard JG, et al, 2004 Does iodine-131 meta-iodobenzylguanidine (MIBG) scintigraphy have an impact on the management of sporadic and familial phaeochromocytoma? Clin Endocrinol 61: 102–108.CrossRefGoogle Scholar
  37. 37.
    Maurea S, Klain M, Mainolfi C, Ziviello M, Salvatore M, 2001 The diagnostic role of radionuclide imaging in evaluation of patients with non-hypersecreting adrenal masses. J Nucl Med 42: 884–892.PubMedGoogle Scholar
  38. 38.
    De Graaf JS, Dullaart RP, Kok T, Piers DA, Zwierstra RP, 2000 Limited role of meta-iodobenzylguanidine scintigraphy in imaging phaeochromocytoma in patients with multiple endocrine neoplasia type II. Eur J Surg 166: 289–292.CrossRefGoogle Scholar
  39. 39.
    Fukuoka M, Taki J, Mochizuki T, Kinuya S, 2011 Comparison of diagnostic value of I-123 MIBG and high-dose I-131 MIBG scintigraphy including incremental value of SPECT/CT over planar image in patients with malignant pheochromocytoma/paraganglioma and neuroblastoma. Clin Nucl Med 36: 1–7.CrossRefGoogle Scholar
  40. 40.
    Kayano D, Taki J, Fukuoka M, et al, 2011 Low-dose (123)I-metaiodobenzylguanidine diagnostic scan is inferior to (131)I-metaiodobenzylguanidine posttreatment scan in detection of malignant pheochromocytoma and paraganglioma. Nucl Med Commun 32: 941–946.CrossRefGoogle Scholar
  41. 41.
    Wiseman GA, Pacak K, O’Dorisio Ms, et al, 2009 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 50: 1448–1454.CrossRefGoogle Scholar
  42. 42.
    Jacobson AF, Deng H, Lombard J, Lessig HJ, Black RR, 2010 123I-meta-iodobenzylguanidine scintigraphy for the detection of neuroblastoma and pheochromocytoma: results of a meta-analysis. J Clin Endocrinol Metab 95: 2596–2606.CrossRefGoogle Scholar
  43. 43.
    Fottner C, Helisch A, Anlauf M, et al, 2010 6-18F-fluoro-L-dihydroxyphenylalanine positron emission tomography is superior to 123I-metaiodobenzyl-guanidine scintigraphy in the detection of extraadrenal and hereditary pheochromocytomas and paragangliomas: correlation with vesicular monoamine transporter expression. J Clin Endocrinol Metab 95: 2800–2810.CrossRefGoogle Scholar
  44. 44.
    Ilias I, Yu J, Carrasquillo JA, et al, 2003 Superiority of 6-[18F]-fluorodopamine positron emission tomography versus [131I]-metaiodobenzylguanidine scintigraphy in the localization of metastatic pheochromocytoma. J Clin Endocrinol Metab 88: 4083–4087.CrossRefGoogle Scholar
  45. 45.
    King KS, Chen CC, Alexopoulos DK, et al, 2011 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 96: 2779–2785.CrossRefGoogle Scholar
  46. 46.
    Kaji P, Carrasquillo JA, Linehan WM, et al, 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.CrossRefGoogle Scholar
  47. 47.
    Timmers HJ, Kozupa A, Chen CC, et al, 2007 Superiority of fluorodeoxyglucose positron emission tomography to other functional imaging techniques in the evaluation of metastatic SDHB-associated pheochromocytoma and paraganglioma. J Clin Oncol 25: 2262–2269.CrossRefGoogle Scholar
  48. 48.
    Fonte JS, Robles JF, Chen CC, et al, 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.CrossRefGoogle Scholar
  49. 49.
    Koopmans KP, Jager PL, Kema IP, Kerstens MN, Albers F, Dullaart RP, 2008 111In-octreotide is superior to 123I-metaiodobenzylguanidine for scintigraphic detection of head and neck paragangliomas. J Nucl Med 49: 1232–1237.CrossRefGoogle Scholar
  50. 50.
    Tenenbaum F, Lumbroso J, Schlumberger M, 1995 Comparison of radiolabeled octreotide and meta-io-dobenzylguanidine (MIBG) scintigraphy in malignant pheochromocytoma. J Nucl Med 36: 1–6.PubMedGoogle Scholar
  51. 51.
    van der Harst E, de Herder WW, Bruining HA, et al, 2001. [(123)I]metaiodobenzylguanidine and [(111)In]octreotide uptake in begnign and malignant pheochromocytomas. J Clin Endocrinol Metab 86: 685–693.Google Scholar
  52. 52.
    Ilias I, Chen CC, Carrasquillo JA, et al, 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.CrossRefGoogle Scholar
  53. 53.
    Pacak K, Eisenhofer G, Goldstein Ds, 2004 Functional imaging of endocrine tumors: role of positron emission tomography. Endocr Rev 25: 568–580.CrossRefGoogle Scholar
  54. 54.
    Cuccurullo V, Mansi L, 2012 Toward tailored medicine (and beyond): the phaeochromocytoma and paraganglioma model. Eur J Nucl Med Mol Imaging 39: 1262–1265.CrossRefGoogle Scholar
  55. 55.
    Lopci E, Chiti A, Castellani MR, et al, 2011 Matched pairs dosimetry: 124I/131I metaiodobenzylguanidine and 124I/131I and 86Y/90Y antibodies. Eur J Nucl Med Mol Imaging 38: suppl 1: 28–40.CrossRefGoogle Scholar
  56. 56.
    Taïeb D, Sebag F, Barlier A, et al, 2009 18F-FDG avidity of pheochromocytomas and paragangliomas: a new molecular imaging signature? J Nucl Med 50: 711–717.CrossRefGoogle Scholar
  57. 57.
    Shulkin BL, Wieland DM, Schwaiger M, et al, 1992 PET scanning with hydroxyephedrine: an approach to the localization of pheochromocytoma. J Nucl Med 33: 1125–1131.PubMedGoogle Scholar
  58. 58.
    Franzius C, Hermann K, Weckesser M, et al, 2006 Whole-body PET/CT with 11C-meta-hydroxyephedrine in tumors of the sympathetic nervous system: feasibility study and comparison with 123I-MIBG SPECT/CT. J Nucl Med 47: 1635–1642.PubMedGoogle Scholar
  59. 59.
    Mann GN, Link JM, Pham P, et al, 2006 [11C]metahydroxyephedrine and [18F]fluorodeoxyglucose positron emission tomography improve clinical decision making in suspected pheochromocytoma. Ann Surg Oncol 13: 187–197.CrossRefGoogle Scholar
  60. 60.
    Mamede M, Carrasquillo JA, Chen CC, et al, 2006 Discordant localization of 2-[18F]-fluoro-2-deoxy-D-glucose in 6-[18F]-fluorodopamine-and [123I]-metaiodobenzylguanidine-negative metastatic pheochromocytoma sites. Nucl Med Commun 27: 31–36.CrossRefGoogle Scholar
  61. 61.
    Zelinka T, Timmers HJ, Kozupa A, et al, 2008 Role of positron emission tomography and bone scintigraphy in the evaluation of bone involvement in metastatic pheochromocytoma and paraganglioma: specific implications for succinate dehydrogenase enzyme subunit B gene mutations. Endocr Relat Cancer 15: 311–323.CrossRefGoogle Scholar
  62. 62.
    Timmers HJ, Chen CC, Carrasquillo JA, et al, 2009 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.CrossRefGoogle Scholar
  63. 63.
    Timmers HJ, Eisenhofer G, Carrasquillo JA, et al, 2009 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) 71: 11–17.CrossRefGoogle Scholar
  64. 64.
    Hoegerle S, Nitzsche E, Altehoefer C, et al, 2002 Pheochromocytomas: detection with 18F DOPA whole body PET-initial results. Radiology 222: 507–512.CrossRefGoogle Scholar
  65. 65.
    Taïeb D, Tessonnier L, Sebag F, et al, 2008 The role of 18F-FDOPA and 18F-FDG-PET in the management of malignant and multifocal phaeochromocytomas. Clin Endocrinol (Oxf) 69: 580–586.CrossRefGoogle Scholar
  66. 66.
    Fiebrich HB, Brouwers AH, Kerstens MN, et al, 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.CrossRefGoogle Scholar
  67. 67.
    Rufini V, Treglia G, Castaldi P, et al, 2011 Comparison of 123I-MIBG SPECT-CT and 18F-DOPA PET-CT in the evaluation of patients with known or suspected recurrent paraganglioma. Nucl Med Commun 32: 575–582.CrossRefGoogle Scholar
  68. 68.
    Shulkin BL, Thompson NW, Shapiro B, Francis IR, Sisson JC, 1999 Pheochromocytomas: imaging with 2-[fluorine-18]fluoro-2-deoxy-D-glucose PET. Radiology 212: 35–41.CrossRefGoogle Scholar
  69. 69.
    Takano A, Oriuchi N, Tsushima Y, et al, 2008 Detection of metastatic lesions from malignant pheochromocytoma and paraganglioma with diffusion-weighted magnetic resonance imaging: comparison with 18F-FDG positron emission tomography and 123I-MIBG scintigraphy. Ann Nucl Med 22: 395–401.CrossRefGoogle Scholar
  70. 70.
    Timmers HJ, Chen CC, Carrasquillo JA, et al, 2012 Staging and functional characterization of pheochromocytoma and paraganglioma by 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography. J Natl Cancer Inst 104: 700–708.CrossRefGoogle Scholar
  71. 71.
    Nakano S, Tsushima Y, Higuchi T, Taketomi-Takahashi A, Amanuma M, 2012 Contrast-and non-contrast-enhanced ultrasonography (US) findings of hepatic metastasis from malignant pheochromocytoma/paraganglioma. Jpn J Radiol 30: 310–316.CrossRefGoogle Scholar
  72. 72.
    Win Z, Al-Nahhas A, Towey D, et al, 2007 68Ga-DOTATATE PET in neuroectodermal tumours: first experience. Nucl Med Commun 28: 359–363.CrossRefGoogle Scholar
  73. 73.
    Kroiss A, Putzer D, Uprimny C, et al, 2011 Functional imaging in phaeochromocytoma and neuroblastoma with 68Ga-DOTA-Tyr 3-octreotide positron emission tomography and 123I-metaiodobenzylguanidine. Eur J Nucl Med Mol Imaging 38: 865–873.CrossRefGoogle Scholar
  74. 74.
    Naji M, Zhao C, Welsh SJ, et al, 2011 68Ga-DOTA-TATE PET vs. 123I-MIBG in identifying malignant neural crest tumours. Mol Imaging Biol 13: 769–775.CrossRefGoogle Scholar
  75. 75.
    Naswa N, Sharma P, Nazar AH, et al, 2012 Prospective evaluation of 68Ga-DOTA-NOC PET-CT in phaeochromocytoma and paraganglioma: preliminary results from a single centre study. Eur Radiol 22: 710–719.CrossRefGoogle Scholar
  76. 76.
    Maurice JB, Troke R, Win Z, et al, 2012 A comparison of the performence of 68Ga-DOTATATE PET/CT and 123I-MIBG SPECT in the diagnosis and follow-up of phaeochromocytoma and paraganglioma. Eur J Nucl Med Mol Imaging 39: 1266–1270.CrossRefGoogle Scholar
  77. 77.
    Taïeb D, Rubello D, Al-Nahhas A, Calzada M, Marzola MC, Hindié E, 2011 Modern PET imaging for paragangliomas: relation to genetic mutations. Eur J Surg Oncol 37: 662–668.CrossRefGoogle Scholar

Copyright information

© Hellenic Endocrine Society 2013

Authors and Affiliations

  • Vittoria Rufini
    • 1
  • Giorgio Treglia
    • 1
  • Germano Perotti
    • 1
  • Alessandro Giordano
    • 1
  1. 1.Istituto di Medicina NucleareUniversità Cattolica del Sacro CuoreRomaItaly

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