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Current Consensus on I-131 MIBG Therapy

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Abstract

Metaiodobenzylguanidine (MIBG) is structurally similar to the neurotransmitter norepinephrine and specifically targets neuroendocrine cells including some neuroendocrine tumors. Iodine-131 (I-131)-labeled MIBG (I-131 MIBG) therapy for neuroendocrine tumors has been performed for more than a quarter-century. The indications of I-131 MIBG therapy include treatment-resistant neuroblastoma (NB), unresectable or metastatic pheochromocytoma (PC) and paraganglioma (PG), unresectable or metastatic carcinoid tumors, and unresectable or metastatic medullary thyroid cancer (MTC). I-131 MIBG therapy is one of the considerable effective treatments in patients with advanced NB, PC, and PG. On the other hand, I-131 MIBG therapy is an alternative method after more effective novel therapies are used such as radiolabeled somatostatin analogs and tyrosine kinase inhibitors in patients with advanced carcinoid tumors and MTC. No-carrier-aided (NCA) I-131 MIBG has more favorable potential compared to the conventional I-131 MIBG. Astatine-211-labeled meta-astatobenzylguanidine (At-211 MABG) has massive potential in patients with neuroendocrine tumors. Further studies about the therapeutic protocols of I-131 MIBG including NCA I-131 MIBG in the clinical setting and At-211 MABG in both the preclinical and clinical settings are needed.

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References

  1. Wieland DM, Wu J, Brown LE, Mangner TJ, Swanson DP, Beierwaltes WH. Radiolabeled adrenergi neuron-blocking agents: adrenomedullary imaging with [131I]iodobenzylguanidine. J Nucl Med. 1980;21:349–53.

    PubMed  CAS  Google Scholar 

  2. McEwan AJ, Shapiro B, Sisson JC, Beierwaltes WH, Ackery DM. Radio-iodobenzylguanidine for the scintigraphic location and therapy of adrenergic tumors. Semin Nucl Med. 1985;15:132–53.

    Article  PubMed  CAS  Google Scholar 

  3. Nakajo M, Shapiro B, Copp J, Kalff V, Gross MD, Sisson JC, et al. The normal and abnormal distribution of the adrenomedullary imaging agent m-[I-131]iodobenzylguanidine (I-131 MIBG) in man: evaluation by scintigraphy. J Nucl Med. 1983;24:672–82.

    PubMed  CAS  Google Scholar 

  4. Sisson J, Shapiro B, Beierwaltes WH, Nakajo M, Glowniak J, Mangner T, et al. Treatment of malignant pheochromocytoma with a new radiopharmaceutical. Trans Assoc Am Phys. 1983;96:209–17.

    PubMed  CAS  Google Scholar 

  5. Treuner J, Klingebiel T, Feine U, Buck J, Bruchelt G, Dopfer R, et al. Clinical experiences in the treatment of neuroblastoma with 131I-metaiodobenzylguanidine. Pediatr Hematol Oncol. 1986;3:205–16.

    Article  PubMed  CAS  Google Scholar 

  6. Hoefnagel CA, Den Hartog Jager FC, Van Gennip AH, Marcuse HR, Taal BG. Diagnosis and treatment of a carcinoid tumor using iodine-131 meta-iodobenzylguanidine. Clin Nucl Med. 1986;11:150–2.

    Article  PubMed  CAS  Google Scholar 

  7. Jaques S Jr, Tobes MC, Sisson JC, Baker JA, Wieland DM. Comparison of the sodium dependency of uptake of meta-lodobenzylguanidine and norepinephrine into cultured bovine adrenomedullary cells. Mol Pharmacol. 1984;26:539–46.

    PubMed  CAS  Google Scholar 

  8. Tobes MC, Jaques S Jr, Wieland DM, Sisson JC. Effect of uptake-one inhibitors on the uptake of norepinephrine and metaiodobenzylguanidine. J Nucl Med. 1985;26:897–907.

    PubMed  CAS  Google Scholar 

  9. Jaques S Jr, Tobes MC, Sisson JC. Sodium dependency of uptake of norepinephrine and m-iodobenzylguanidine into cultured human pheochromocytoma cells: evidence for uptake-one. Cancer Res. 1987;47:3920–8.

    PubMed  Google Scholar 

  10. Buck J, Bruchelt G, Girgert R, Treuner J, Niethammer D. Specific uptake of m-[125I]iodobenzylguanidine in the human neuroblastoma cell line SK-N-SH. Cancer Res. 1985;45:6366–70.

    PubMed  CAS  Google Scholar 

  11. Smets LA, Loesberg C, Janssen M, Metwally EA, Huiskamp R. Active uptake and extravesicular storage of m-iodobenzylguanidine in human neuroblastoma SK-N-SH cells. Cancer Res. 1989;49:2941–4.

    PubMed  CAS  Google Scholar 

  12. Kolby L, Bernhardt P, Levin-Jakobsen AM, Johanson V, Wangberg B, Ahlman H, et al. Uptake of meta-iodobenzylguanidine in neuroendocrine tumours is mediated by vesicular monoamine transporters. Br J Cancer. 2003;89:1383–8.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  13. Nilsson O, Jakobsen AM, Kolby L, Bernhardt P, Forssell-Aronsson E, Ahlman H. Importance of vesicle proteins in the diagnosis and treatment of neuroendocrine tumors. Ann N Y Acad Sci. 2004;1014:280–3.

    Article  PubMed  CAS  Google Scholar 

  14. Lashford LS, Hancock JP, Kemshead JT. Meta-iodobenzylguanidine (mIBG) uptake and storage in the human neuroblastoma cell line SK-N-BE(2C). Int J Cancer. 1991;47:105–9.

    Article  PubMed  CAS  Google Scholar 

  15. Gaze MN, Huxham IM, Mairs RJ, Barrett A. Intracellular localization of metaiodobenzyl guanidine in human neuroblastoma cells by electron spectroscopic imaging. Int J Cancer. 1991;47:875–80.

    Article  PubMed  CAS  Google Scholar 

  16. Giammarile F, Chiti A, Lassmann M, Brans B, Flux G. EANM procedure guidelines for 131I-meta-iodobenzylguanidine (131I-mIBG) therapy. Eur J Nucl Med Mol Imaging. 2008;35:1039–47.

    Article  PubMed  CAS  Google Scholar 

  17. Kinuya S, Yoshinaga K, Higuchi T, Jinguji M, Kurihara H, Kawamoto H. Draft guidelines regarding appropriate use of (131)I-MIBG radiotherapy for neuroendocrine tumors: guideline drafting Committee for Radiotherapy with (131)I-MIBG, Committee for Nuclear Oncology and Immunology, the Japanese Society of Nuclear Medicine. Ann Nucl Med. 2015;29:543–52.

    Article  PubMed  CAS  Google Scholar 

  18. Verger P, Aurengo A, Geoffroy B, Le Guen B. Iodine kinetics and effectiveness of stable iodine prophylaxis after intake of radioactive iodine: a review. Thyroid. 2001;11:353–60.

    Article  PubMed  CAS  Google Scholar 

  19. van Santen HM, de Kraker J, van Eck BL, de Vijlder JJ, Vulsma T. Improved radiation protection of the thyroid gland with thyroxine, methimazole, and potassium iodide during diagnostic and therapeutic use of radiolabeled metaiodobenzylguanidine in children with neuroblastoma. Cancer. 2003;98:389–96.

    Article  PubMed  CAS  Google Scholar 

  20. Quach A, Ji L, Mishra V, Sznewajs A, Veatch J, Huberty J, et al. Thyroid and hepatic function after high-dose 131 I-metaiodobenzylguanidine (131 I-MIBG) therapy for neuroblastoma. Pediatr Blood Cancer. 2011;56:191–201.

    Article  PubMed  Google Scholar 

  21. DuBois SG, Messina J, Maris JM, Huberty J, Glidden DV, Veatch J, et al. Hematologic toxicity of high-dose iodine-131-metaiodobenzylguanidine therapy for advanced neuroblastoma. J Clin Oncol. 2004;22:2452–60.

    Article  PubMed  CAS  Google Scholar 

  22. Matthay KK, DeSantes K, Hasegawa B, Huberty J, Hattner RS, Ablin A, et al. Phase I dose escalation of 131I-metaiodobenzylguanidine with autologous bone marrow support in refractory neuroblastoma. J Clin Oncol. 1998;16:229–36.

    Article  PubMed  CAS  Google Scholar 

  23. Matthay KK, Yanik G, Messina J, Quach A, Huberty J, Cheng SC, et al. Phase II study on the effect of disease sites, age, and prior therapy on response to iodine-131-metaiodobenzylguanidine therapy in refractory neuroblastoma. J Clin Oncol. 2007;25:1054–60.

    Article  PubMed  CAS  Google Scholar 

  24. Gonias S, Goldsby R, Matthay KK, Hawkins R, Price D, Huberty J, et al. Phase II study of high-dose [131I]metaiodobenzylguanidine therapy for patients with metastatic pheochromocytoma and paraganglioma. J Clin Oncol. 2009;27:4162–8.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  25. Kayano D, Kinuya S. Iodine-131 metaiodobenzylguanidine therapy for neuroblastoma: reports so far and future perspective. ScientificWorldJournal. 2015;2015:189135.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  26. Bleeker G, Schoot RA, Caron HN, de Kraker J, Hoefnagel CA, van Eck BL, et al. Toxicity of upfront (1)(3)(1)I-metaiodobenzylguanidine ((1)(3)(1)I-MIBG) therapy in newly diagnosed neuroblastoma patients: a retrospective analysis. Eur J Nucl Med Mol Imaging. 2013;40:1711–7.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  27. Modak S, Pandit-Taskar N, Kushner BH, Kramer K, Smith-Jones P, Larson S, et al. Transient sialoadenitis: a complication of 131I-metaiodobenzylguanidine therapy. Pediatr Blood Cancer. 2008;50:1271–3.

    Article  PubMed  Google Scholar 

  28. van Santen HM, de Kraker J, van Eck BL, de Vijlder JJ, Vulsma T. High incidence of thyroid dysfunction despite prophylaxis with potassium iodide during (131)I-meta-iodobenzylguanidine treatment in children with neuroblastoma. Cancer. 2002;94:2081–9.

    Article  PubMed  CAS  Google Scholar 

  29. Clement SC, van Eck-Smit BL, van Trotsenburg AS, Kremer LC, Tytgat GA, van Santen HM. Long-term follow-up of the thyroid gland after treatment with 131I-Metaiodobenzylguanidine in children with neuroblastoma: importance of continuous surveillance. Pediatr Blood Cancer. 2013;60:1833–8.

    Article  PubMed  CAS  Google Scholar 

  30. Huibregtse KE, Vo KT, DuBois SG, Fetzko S, Neuhaus J, Batra V, et al. Incidence and risk factors for secondary malignancy in patients with neuroblastoma after treatment with (131)I-metaiodobenzylguanidine. Eur J Cancer. 2016;66:144–52.

    Article  PubMed  CAS  Google Scholar 

  31. Garaventa A, Gambini C, Villavecchia G, Di Cataldo A, Bertolazzi L, Pizzitola MR, et al. Second malignancies in children with neuroblastoma after combined treatment with 131I-metaiodobenzylguanidine. Cancer. 2003;97:1332–8.

    Article  PubMed  CAS  Google Scholar 

  32. Weiss B, Vora A, Huberty J, Hawkins RA, Matthay KK. Secondary myelodysplastic syndrome and leukemia following 131I-metaiodobenzylguanidine therapy for relapsed neuroblastoma. J Pediatr Hematol Oncol. 2003;25(7):543.

    Article  PubMed  Google Scholar 

  33. Bonisch H, Bruss M. The norepinephrine transporter in physiology and disease. Handb Exp Pharmacol. 2006;175:485–524.

    Article  Google Scholar 

  34. Maris JM. Recent advances in neuroblastoma. N Engl J Med. 2010;362:2202–11.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  35. London WB, Castleberry RP, Matthay KK, Look AT, Seeger RC, Shimada H, et al. Evidence for an age cutoff greater than 365 days for neuroblastoma risk group stratification in the Children’s oncology group. J Clin Oncol. 2005;23:6459–65.

    Article  PubMed  CAS  Google Scholar 

  36. Voo S, Bucerius J, Mottaghy FM. I-131-MIBG therapies. Methods. 2011;55:238–45.

    Article  PubMed  CAS  Google Scholar 

  37. Maris JM, Hogarty MD, Bagatell R, Cohn SL. Neuroblastoma. Lancet. 2007;369:2106–20.

    Article  PubMed  CAS  Google Scholar 

  38. Brodeur GM, Pritchard J, Berthold F, Carlsen NL, Castel V, Castelberry RP, et al. Revisions of the international criteria for neuroblastoma diagnosis, staging, and response to treatment. J Clin Oncol. 1993;11:1466–77.

    Article  PubMed  CAS  Google Scholar 

  39. Matthay KK, Villablanca JG, Seeger RC, Stram DO, Harris RE, Ramsay NK, et al. Treatment of high-risk neuroblastoma with intensive chemotherapy, radiotherapy, autologous bone marrow transplantation, and 13-cis-retinoic acid. Children's Cancer group. N Engl J Med. 1999;341:1165–73.

    Article  PubMed  CAS  Google Scholar 

  40. Berthold F, Boos J, Burdach S, Erttmann R, Henze G, Hermann J, et al. Myeloablative megatherapy with autologous stem-cell rescue versus oral maintenance chemotherapy as consolidation treatment in patients with high-risk neuroblastoma: a randomised controlled trial. Lancet Oncol. 2005;6:649–58.

    Article  PubMed  CAS  Google Scholar 

  41. Mueller S, Matthay KK. Neuroblastoma: biology and staging. Curr Oncol Rep. 2009;11:431–8.

    Article  PubMed  Google Scholar 

  42. Treuner J, Feine U, Niethammer D, Muller-Schaumburg W, Meinke J, Eibach E, et al. Scintigraphic imaging of neuroblastoma with [131-I]iodobenzylguanidine. Lancet. 1984;1:333–4.

    Article  PubMed  CAS  Google Scholar 

  43. Carlin S, Mairs RJ, McCluskey AG, Tweddle DA, Sprigg A, Estlin C, et al. Development of a real-time polymerase chain reaction assay for prediction of the uptake of meta-[(131)I]iodobenzylguanidine by neuroblastoma tumors. Clin Cancer Res. 2003;9:3338–44.

    PubMed  CAS  Google Scholar 

  44. Hoefnagel CA, Voute PA, De Kraker J, Valdes Olmos RA. [131I]metaiodobenzylguanidine therapy after conventional therapy for neuroblastoma. J Nucl Biol Med. 1991;35:202–6.

    PubMed  CAS  Google Scholar 

  45. Lumbroso J, Hartmann O, Schlumberger M. Therapeutic use of [131I]metaiodobenzylguanidine in neuroblastoma: a phase II study in 26 patients. “Societe Francaise d'Oncologie Pediatrique” and nuclear medicine co-investigators. J Nucl Biol Med. 1991;35:220–3.

    PubMed  CAS  Google Scholar 

  46. Matthay KK, Huberty JP, Hattner RS, Ablin AR, Engelstad BL, Zoger S, et al. Efficacy and safety of [131I]metaiodobenzylguanidine therapy for patients with refractory neuroblastoma. J Nucl Biol Med. 1991;35:244–7.

    PubMed  CAS  Google Scholar 

  47. Garaventa A, Bellagamba O, Lo Piccolo MS, Milanaccio C, Lanino E, Bertolazzi L, et al. 131I-metaiodobenzylguanidine (131I-MIBG) therapy for residual neuroblastoma: a mono-institutional experience with 43 patients. Br J Cancer. 1999;81:1378–84.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  48. Weyl Ben-Arush M, Ben Barak A, Bar-Deroma R, Ash S, Goldstein G, Golan H, et al. Targeted therapy with low doses of 131I-MIBG is effective for disease palliation in highly refractory neuroblastoma. Isr Med Assoc J. 2013;15:31–4.

    PubMed  Google Scholar 

  49. Mastrangelo S, Tornesello A, Diociaiuti L, Pession A, Prete A, Rufini V, et al. Treatment of advanced neuroblastoma: feasibility and therapeutic potential of a novel approach combining 131-I-MIBG and multiple drug chemotherapy. Br J Cancer. 2001;84(4):460.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  50. DuBois SG, Chesler L, Groshen S, Hawkins R, Goodarzian F, Shimada H, et al. Phase I study of vincristine, irinotecan, and (1)(3)(1)I-metaiodobenzylguanidine for patients with relapsed or refractory neuroblastoma: a new approaches to neuroblastoma therapy trial. Clin Cancer Res. 2012;18:2679–86.

    Article  PubMed  CAS  Google Scholar 

  51. DuBois SG, Allen S, Bent M, Hilton JF, Hollinger F, Hawkins R, et al. Phase I/II study of (131)I-MIBG with vincristine and 5 days of irinotecan for advanced neuroblastoma. Br J Cancer. 2015;112:644–9.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  52. DuBois SG, Groshen S, Park JR, Haas-Kogan DA, Yang X, Geier E, et al. Phase I study of Vorinostat as a radiation sensitizer with 131I-Metaiodobenzylguanidine (131I-MIBG) for patients with relapsed or refractory neuroblastoma. Clin Cancer Res. 2015;21:2715–21.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  53. Modak S, Zanzonico P, Carrasquillo JA, Kushner BH, Kramer K, Cheung NK, et al. Arsenic trioxide as a radiation sensitizer for 131I-metaiodobenzylguanidine therapy: results of a phase II study. J Nucl Med. 2016;57:231–7.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  54. Ning S, Knox SJ. Increased cure rate of glioblastoma using concurrent therapy with radiotherapy and arsenic trioxide. Int J Radiat Oncol Biol Phys. 2004;60:197–203.

    Article  PubMed  CAS  Google Scholar 

  55. Chiu HW, Lin JH, Chen YA, Ho SY, Wang YJ. Combination treatment with arsenic trioxide and irradiation enhances cell-killing effects in human fibrosarcoma cells in vitro and in vivo through induction of both autophagy and apoptosis. Autophagy. 2010;6:353–65.

    Article  PubMed  CAS  Google Scholar 

  56. Gaze MN, Wheldon TE, O'Donoghue JA, Hilditch TE, McNee SG, Simpson E, et al. Multi-modality megatherapy with [131I]meta-iodobenzylguanidine, high dose melphalan and total body irradiation with bone marrow rescue: feasibility study of a new strategy for advanced neuroblastoma. Eur J Cancer. 1995;31a:252–6.

    Article  PubMed  CAS  Google Scholar 

  57. Klingebiel T, Bader P, Bares R, Beck J, Hero B, Jurgens H, et al. Treatment of neuroblastoma stage 4 with 131I-meta-iodo-benzylguanidine, high-dose chemotherapy and immunotherapy. A pilot study. Eur J Cancer. 1998;34:1398–402.

    Article  PubMed  CAS  Google Scholar 

  58. Miano M, Garaventa A, Pizzitola MR, Piccolo MS, Dallorso S, Villavecchia GP, et al. Megatherapy combining I(131) metaiodobenzylguanidine and high-dose chemotherapy with haematopoietic progenitor cell rescue for neuroblastoma. Bone Marrow Transplant. 2001;27:571–4.

    Article  PubMed  CAS  Google Scholar 

  59. Matthay KK, Tan JC, Villablanca JG, Yanik GA, Veatch J, Franc B, et al. Phase I dose escalation of iodine-131-metaiodobenzylguanidine with myeloablative chemotherapy and autologous stem-cell transplantation in refractory neuroblastoma: a new approaches to neuroblastoma therapy consortium study. J Clin Oncol. 2006;24:500–6.

    Article  PubMed  CAS  Google Scholar 

  60. Yanik GA, Villablanca JG, Maris JM, Weiss B, Groshen S, Marachelian A, et al. 131I-metaiodobenzylguanidine with intensive chemotherapy and autologous stem cell transplantation for high-risk neuroblastoma. A new approaches to neuroblastoma therapy (NANT) phase II study. Biol Blood Marrow Transplant. 2015;21:673–81.

    Article  PubMed  CAS  Google Scholar 

  61. French S, DuBois SG, Horn B, Granger M, Hawkins R, Pass A, et al. 131I-MIBG followed by consolidation with busulfan, melphalan and autologous stem cell transplantation for refractory neuroblastoma. Pediatr Blood Cancer. 2013;60:879–84.

    Article  PubMed  CAS  Google Scholar 

  62. Zhou MJ, Doral MY, DuBois SG, Villablanca JG, Yanik GA, Matthay KK. Different outcomes for relapsed versus refractory neuroblastoma after therapy with (131)I-metaiodobenzylguanidine ((131)I-MIBG). Eur J Cancer. 2015;51:2465–72.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  63. Mastrangelo S, Rufini V, Ruggiero A, Di Giannatale A, Riccardi R. Treatment of advanced neuroblastoma in children over 1 year of age: the critical role of (1)(3)(1)I-metaiodobenzylguanidine combined with chemotherapy in a rapid induction regimen. Pediatr Blood Cancer. 2011;56:1032–40.

    Article  PubMed  Google Scholar 

  64. Kraal KC, Tytgat GA, van Eck-Smit BL, Kam B, Caron HN, van Noesel M. Upfront treatment of high-risk neuroblastoma with a combination of 131I-MIBG and topotecan. Pediatr Blood Cancer. 2015;62:1886–91.

    Article  PubMed  CAS  Google Scholar 

  65. Kraal KC, Bleeker GM, van Eck-Smit BL, van Eijkelenburg NK, Berthold F, van Noesel MM, et al. Feasibility, toxicity and response of upfront metaiodobenzylguanidine therapy followed by German pediatric oncology group neuroblastoma 2004 protocol in newly diagnosed stage 4 neuroblastoma patients. Eur J Cancer. 2017;76:188–96.

    Article  PubMed  CAS  Google Scholar 

  66. Lee JW, Lee S, Cho HW, Ma Y, Yoo KH, Sung KW, et al. Incorporation of high-dose 131I-metaiodobenzylguanidine treatment into tandem high-dose chemotherapy and autologous stem cell transplantation for high-risk neuroblastoma: results of the SMC NB-2009 study. J Hematol Oncol. 2017;10:108.

    Article  PubMed  PubMed Central  Google Scholar 

  67. Sung KW, Son MH, Lee SH, Yoo KH, Koo HH, Kim JY, et al. Tandem high-dose chemotherapy and autologous stem cell transplantation in patients with high-risk neuroblastoma: results of SMC NB-2004 study. Bone Marrow Transplant. 2013;48:68–73.

    Article  PubMed  CAS  Google Scholar 

  68. Gains JE, Bomanji JB, Fersht NL, Sullivan T, D'Souza D, Sullivan KP, et al. 177Lu-DOTATATE molecular radiotherapy for childhood neuroblastoma. J Nucl Med. 2011;52(7):1041.

    Article  PubMed  Google Scholar 

  69. Kong G, Hofman MS, Murray WK, Wilson S, Wood P, Downie P, et al. Initial experience with gallium-68 DOTA-Octreotate PET/CT and peptide receptor radionuclide therapy for pediatric patients with refractory metastatic neuroblastoma. J Pediatr Hematol Oncol. 2016;38:87–96.

    Article  PubMed  CAS  Google Scholar 

  70. Lam AK. Update on adrenal tumours in 2017 World Health Organization (WHO) of endocrine tumours. Endocr Pathol. 2017;28:213–27.

    Article  PubMed  Google Scholar 

  71. Beard CM, Sheps SG, Kurland LT, Carney JA, Lie JT. Occurrence of pheochromocytoma in Rochester, Minnesota, 1950 through 1979. Mayo Clin Proc. 1983;58:802–4.

    PubMed  CAS  Google Scholar 

  72. Stenstrom G, Svardsudd K. Pheochromocytoma in Sweden 1958-1981. An analysis of the National Cancer Registry data. Acta Med Scand. 1986;220:225–32.

    Article  PubMed  CAS  Google Scholar 

  73. Andersen GS, Toftdahl DB, Lund JO, Strandgaard S, Nielsen PE. The incidence rate of phaeochromocytoma and Conn’s syndrome in Denmark, 1977-1981. J Hum Hypertens. 1988;2:187–9.

    PubMed  CAS  Google Scholar 

  74. Guerrero MA, Schreinemakers JM, Vriens MR, Suh I, Hwang J, Shen WT, et al. Clinical spectrum of pheochromocytoma. J Am Coll Surg. 2009;209:727–32.

    Article  PubMed  Google Scholar 

  75. Sutton MG, Sheps SG, Lie JT. Prevalence of clinically unsuspected pheochromocytoma. Review of a 50-year autopsy series. Mayo Clin Proc. 1981;56:354–60.

    PubMed  CAS  Google Scholar 

  76. Ezzat Abdel-Aziz T, Prete F, Conway G, Gaze M, Bomanji J, Bouloux P, et al. Phaeochromocytomas and paragangliomas: a difference in disease behaviour and clinical outcomes. J Surg Oncol. 2015;112:486–91.

    Article  PubMed  Google Scholar 

  77. Amar L, Baudin E, Burnichon N, Peyrard S, Silvera S, Bertherat J, et al. Succinate dehydrogenase B gene mutations predict survival in patients with malignant pheochromocytomas or paragangliomas. J Clin Endocrinol Metab. 2007;92:3822–8.

    Article  PubMed  CAS  Google Scholar 

  78. Szalat A, Fraenkel M, Doviner V, Salmon A, Gross DJ. Malignant pheochromocytoma: predictive factors of malignancy and clinical course in 16 patients at a single tertiary medical center. Endocrine. 2011;39:160–6.

    Article  PubMed  CAS  Google Scholar 

  79. Lloyd RV, Osamura RY, Klöppel G, Rosai J. WHO classification of tumours of endocrine organs. 4th ed. Lyon: International Agency for Research on Cancer; 2017.

    Google Scholar 

  80. 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;50:1448–54.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  81. Shapiro B, Sisson JC, Wieland DM, Mangner TJ, Zempel SM, Mudgett E, et al. Radiopharmaceutical therapy of malignant pheochromocytoma with [131I]metaiodobenzylguanidine: results from ten years of experience. J Nucl Biol Med. 1991;35:269–76.

    PubMed  CAS  Google Scholar 

  82. 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 Investig. 1997;20:648–58.

    Article  CAS  Google Scholar 

  83. Shilkrut M, Bar-Deroma R, Bar-Sela G, Berniger A, Kuten A. Low-dose iodine-131 metaiodobenzylguanidine therapy for patients with malignant pheochromocytoma and paraganglioma: single center experience. Am J Clin Oncol. 2010;33:79–82.

    Article  PubMed  CAS  Google Scholar 

  84. Wakabayashi H, Taki J, Inaki A, Nakamura A, Kayano D, Fukuoka M, et al. Prognostic values of initial responses to low-dose (131)I-MIBG therapy in patients with malignant pheochromocytoma and paraganglioma. Ann Nucl Med. 2013;27:839–46.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  85. Yoshinaga K, Oriuchi N, Wakabayashi H, Tomiyama Y, Jinguji M, Higuchi T, et al. Effects and safety of (1)(3)(1)I-metaiodobenzylguanidine (MIBG) radiotherapy in malignant neuroendocrine tumors: results from a multicenter observational registry. Endocr J. 2014;61:1171–80.

    Article  PubMed  CAS  Google Scholar 

  86. Rutherford MA, Rankin AJ, Yates TM, Mark PB, Perry CG, Reed NS, et al. Management of metastatic phaeochromocytoma and paraganglioma: use of iodine-131-meta-iodobenzylguanidine therapy in a tertiary referral Centre. QJM. 2015;108:361–8.

    Article  PubMed  CAS  Google Scholar 

  87. Safford SD, Coleman RE, Gockerman JP, Moore J, Feldman JM, Leight GS Jr, et al. Iodine -131 metaiodobenzylguanidine is an effective treatment for malignant pheochromocytoma and paraganglioma. Surgery. 2003;134:956–62. discussion 62–3

    Article  PubMed  Google Scholar 

  88. Gedik GK, Hoefnagel CA, Bais E, Olmos RA. 131I-MIBG therapy in metastatic phaeochromocytoma and paraganglioma. Eur J Nucl Med Mol Imaging. 2008;35:725–33.

    Article  PubMed  CAS  Google Scholar 

  89. Rose B, Matthay KK, Price D, Huberty J, Klencke B, Norton JA, et al. High-dose 131I-metaiodobenzylguanidine therapy for 12 patients with malignant pheochromocytoma. Cancer. 2003;98:239–48.

    Article  PubMed  CAS  Google Scholar 

  90. Fitzgerald PA, Goldsby RE, Huberty JP, Price DC, Hawkins RA, Veatch JJ, et al. Malignant pheochromocytomas and paragangliomas: a phase II study of therapy with high-dose 131I-metaiodobenzylguanidine (131I-MIBG). Ann N Y Acad Sci. 2006;1073:465–90.

    Article  PubMed  CAS  Google Scholar 

  91. Lam MG, Lips CJ, Jager PL, Dullaart RP, Lentjes EG, van Rijk PP, et al. Repeated [131I]metaiodobenzylguanidine therapy in two patients with malignant pheochromocytoma. J Clin Endocrinol Metab. 2005;90:5888–95.

    Article  PubMed  CAS  Google Scholar 

  92. Sisson JC, Shapiro B, Shulkin BL, Urba S, Zempel S, Spaulding S. Treatment of malignant pheochromocytomas with 131-I metaiodobenzylguanidine and chemotherapy. Am J Clin Oncol. 1999;22:364–70.

    Article  PubMed  CAS  Google Scholar 

  93. Forrer F, Riedweg I, Maecke HR, Mueller-Brand J. Radiolabeled DOTATOC in patients with advanced paraganglioma and pheochromocytoma. Q J Nucl Med Mol Imaging. 2008;52:334–40.

    PubMed  CAS  Google Scholar 

  94. Kong G, Grozinsky-Glasberg S, Hofman MS, Callahan J, Meirovitz A, Maimon O, et al. Efficacy of peptide receptor radionuclide therapy for functional metastatic paraganglioma and pheochromocytoma. J Clin Endocrinol Metab. 2017;102:3278–87.

    Article  PubMed  Google Scholar 

  95. Nastos K, Cheung VTF, Toumpanakis C, Navalkissoor S, Quigley AM, Caplin M, et al. Peptide receptor radionuclide treatment and (131)I-MIBG in the management of patients with metastatic/progressive phaeochromocytomas and paragangliomas. J Surg Oncol. 2017;115:425–34.

    Article  PubMed  CAS  Google Scholar 

  96. Maggard MA, O'Connell JB, Ko CY. Updated population-based review of carcinoid tumors. Ann Surg. 2004;240:117–22.

    Article  PubMed  PubMed Central  Google Scholar 

  97. Yao JC, Hassan M, Phan A, Dagohoy C, Leary C, Mares JE, et al. One hundred years after “carcinoid”: epidemiology of and prognostic factors for neuroendocrine tumors in 35,825 cases in the United States. J Clin Oncol. 2008;26:3063–72.

    Article  PubMed  Google Scholar 

  98. Hemminki K, Li X. Incidence trends and risk factors of carcinoid tumors: a nationwide epidemiologic study from Sweden. Cancer. 2001;92:2204–10.

    Article  PubMed  CAS  Google Scholar 

  99. Modlin IM, Kidd M, Latich I, Zikusoka MN, Shapiro MD. Current status of gastrointestinal carcinoids. Gastroenterology. 2005;128:1717–51.

    Article  PubMed  Google Scholar 

  100. Halperin DM, Shen C, Dasari A, Xu Y, Chu Y, Zhou S, et al. Frequency of carcinoid syndrome at neuroendocrine tumour diagnosis: a population-based study. Lancet Oncol. 2017;18:525–34.

    Article  PubMed  PubMed Central  Google Scholar 

  101. Strosberg J, Gardner N, Kvols L. Survival and prognostic factor analysis of 146 metastatic neuroendocrine tumors of the mid-gut. Neuroendocrinology. 2009;89:471–6.

    Article  PubMed  CAS  Google Scholar 

  102. Modlin IM, Lye KD, Kidd M. A 5-decade analysis of 13,715 carcinoid tumors. Cancer. 2003;97:934–59.

    Article  PubMed  Google Scholar 

  103. Feldman JM, Blinder RA, Lucas KJ, Coleman RE. Iodine-131 metaiodobenzylguanidine scintigraphy of carcinoid tumors. J Nucl Med. 1986;27:1691–6.

    PubMed  CAS  Google Scholar 

  104. Kaltsas G, Korbonits M, Heintz E, Mukherjee JJ, Jenkins PJ, Chew SL, et al. Comparison of somatostatin analog and meta-iodobenzylguanidine radionuclides in the diagnosis and localization of advanced neuroendocrine tumors. J Clin Endocrinol Metab. 2001;86:895–902.

    Article  PubMed  CAS  Google Scholar 

  105. Le Rest C, Bomanji JB, Costa DC, Townsend CE, Visvikis D, Ell PJ. Functional imaging of malignant paragangliomas and carcinoid tumours. Eur J Nucl Med. 2001;28:478–82.

    Article  PubMed  Google Scholar 

  106. Herrmann K, Czernin J, Wolin EM, Gupta P, Barrio M, Gutierrez A, et al. Impact of 68Ga-DOTATATE PET/CT on the management of neuroendocrine tumors: the referring physician’s perspective. J Nucl Med. 2015;56:70–5.

    Article  PubMed  CAS  Google Scholar 

  107. Imhof A, Brunner P, Marincek N, Briel M, Schindler C, Rasch H, et al. Response, survival, and long-term toxicity after therapy with the radiolabeled somatostatin analogue [90Y-DOTA]-TOC in metastasized neuroendocrine cancers. J Clin Oncol. 2011;29:2416–23.

    Article  PubMed  CAS  Google Scholar 

  108. Brabander T, van der Zwan WA, Teunissen JJM, Kam BLR, Feelders RA, de Herder WW, et al. Long-term efficacy, survival, and safety of [(177)Lu-DOTA(0),Tyr(3)]octreotate in patients with gastroenteropancreatic and bronchial neuroendocrine tumors. Clin Cancer Res. 2017;23:4617–24.

    Article  PubMed  CAS  Google Scholar 

  109. Strosberg J, El-Haddad G, Wolin E, Hendifar A, Yao J, Chasen B, et al. Phase 3 trial of (177)Lu-Dotatate for midgut neuroendocrine tumors. N Engl J Med. 2017;376:125–35.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  110. Grunwald F, Ezziddin S. 131I-metaiodobenzylguanidine therapy of neuroblastoma and other neuroendocrine tumors. Semin Nucl Med. 2010;40:153–63.

    Article  PubMed  Google Scholar 

  111. Sywak MS, Pasieka JL, McEwan A, Kline G, Rorstad O. 131I-meta-iodobenzylguanidine in the management of metastatic midgut carcinoid tumors. World J Surg. 2004;28:1157–62.

    Article  PubMed  Google Scholar 

  112. Safford SD, Coleman RE, Gockerman JP, Moore J, Feldman J, Onaitis MW, et al. Iodine-131 metaiodobenzylguanidine treatment for metastatic carcinoid. Results in 98 patients. Cancer. 2004;101:1987–93.

    Article  PubMed  CAS  Google Scholar 

  113. Nwosu AC, Jones L, Vora J, Poston GJ, Vinjamuri S, Pritchard DM. Assessment of the efficacy and toxicity of (131)I-metaiodobenzylguanidine therapy for metastatic neuroendocrine tumours. Br J Cancer. 2008;98:1053–8.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  114. Ezziddin S, Sabet A, Logvinski T, Alkawaldeh K, Yong-Hing CJ, Ahmadzadehfar H, et al. Long-term outcome and toxicity after dose-intensified treatment with 131I-MIBG for advanced metastatic carcinoid tumors. J Nucl Med. 2013;54:2032–8.

    Article  PubMed  CAS  Google Scholar 

  115. Williams ED. Histogenesis of medullary carcinoma of the thyroid. J Clin Pathol. 1966;19:114–8.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  116. Wells SA Jr, Asa SL, Dralle H, Elisei R, Evans DB, Gagel RF, et al. Revised American Thyroid Association guidelines for the management of medullary thyroid carcinoma. Thyroid. 2015;25:567–610.

    Article  PubMed  PubMed Central  Google Scholar 

  117. Kameyama K, Takami H. Medullary thyroid carcinoma: nationwide Japanese survey of 634 cases in 1996 and 271 cases in 2002. Endocr J. 2004;51:453–6.

    Article  PubMed  CAS  Google Scholar 

  118. Pacini F, Castagna MG, Cipri C, Schlumberger M. Medullary thyroid carcinoma. Clin Oncol (R Coll Radiol). 2010;22:475–85.

    Article  CAS  Google Scholar 

  119. Modigliani E, Cohen R, Campos JM, Conte-Devolx B, Maes B, Boneu A, et al. Prognostic factors for survival and for biochemical cure in medullary thyroid carcinoma: results in 899 patients. The GETC study group. Groupe d'etude des tumeurs a calcitonine. Clin Endocrinol. 1998;48:265–73.

    Article  CAS  Google Scholar 

  120. Ilias I, Divgi C, Pacak K. Current role of metaiodobenzylguanidine in the diagnosis of pheochromocytoma and medullary thyroid cancer. Semin Nucl Med. 2011;41:364–8.

    Article  PubMed  PubMed Central  Google Scholar 

  121. Castellani MR, Seregni E, Maccauro M, Chiesa C, Aliberti G, Orunesu E, et al. MIBG for diagnosis and therapy of medullary thyroid carcinoma: is there still a role? Q J Nucl Med Mol Imaging. 2008;52:430–40.

    PubMed  CAS  Google Scholar 

  122. Gao Z, Biersack HJ, Ezziddin S, Logvinski T, An R. The role of combined imaging in metastatic medullary thyroid carcinoma: 111In-DTPA-octreotide and 131I/123I-MIBG as predictors for radionuclide therapy. J Cancer Res Clin Oncol. 2004;130:649–56.

    Article  PubMed  Google Scholar 

  123. Maiza JC, Grunenwald S, Otal P, Vezzosi D, Bennet A, Caron P. Use of 131 I-MIBG therapy in MIBG-positive metastatic medullary thyroid carcinoma. Thyroid. 2012;22:654–5.

    Article  PubMed  CAS  Google Scholar 

  124. Mairs RJ, Cunningham SH, Russell J, Armour A, Owens J, McKellar K, et al. No-carrier-added iodine-131-MIBG: evaluation of a therapeutic preparation. J Nucl Med. 1995;36:1088–95.

    PubMed  CAS  Google Scholar 

  125. Vaidyanathan G, Zalutsky MR. No-carrier-added synthesis of meta-[131I]iodobenzylguanidine. Appl Radiat Isot. 1993;44:621–8.

    Article  PubMed  CAS  Google Scholar 

  126. Barrett JA, Joyal JL, Hillier SM, Maresca KP, Femia FJ, Kronauge JF, et al. Comparison of high-specific-activity ultratrace 123/131I-MIBG and carrier-added 123/131I-MIBG on efficacy, pharmacokinetics, and tissue distribution. Cancer Biother Radiopharm. 2010;25:299–308.

    Article  PubMed  CAS  Google Scholar 

  127. Coleman RE, Stubbs JB, Barrett JA, de la Guardia M, Lafrance N, Babich JW. Radiation dosimetry, pharmacokinetics, and safety of ultratrace Iobenguane I-131 in patients with malignant pheochromocytoma/paraganglioma or metastatic carcinoid. Cancer Biother Radiopharm. 2009;24:469–75.

    Article  PubMed  CAS  Google Scholar 

  128. Matthay KK, Weiss B, Villablanca JG, Maris JM, Yanik GA, Dubois SG, et al. Dose escalation study of no-carrier-added 131I-metaiodobenzylguanidine for relapsed or refractory neuroblastoma: new approaches to neuroblastoma therapy consortium trial. J Nucl Med. 2012;53:1155–63.

    Article  PubMed  CAS  Google Scholar 

  129. Zalutsky MR, Vaidyanathan G. Astatine-211-labeled radiotherapeutics: an emerging approach to targeted alpha-particle radiotherapy. Curr Pharm Des. 2000;6:1433–55.

    Article  PubMed  CAS  Google Scholar 

  130. Zalutsky MR, Reardon DA, Akabani G, Coleman RE, Friedman AH, Friedman HS, et al. Clinical experience with alpha-particle emitting 211At: treatment of recurrent brain tumor patients with 211At-labeled chimeric antitenascin monoclonal antibody 81C6. J Nucl Med. 2008;49:30–8.

    Article  PubMed  CAS  Google Scholar 

  131. Vaidyanathan G, Zalutsky MR. 1-(m-[211At]astatobenzyl)guanidine: synthesis via astato demetalation and preliminary in vitro and in vivo evaluation. Bioconjug Chem. 1992;3:499–503.

    Article  PubMed  CAS  Google Scholar 

  132. Strickland DK, Vaidyanathan G, Zalutsky MR. Cytotoxicity of alpha-particle-emitting m-[211At]astatobenzylguanidine on human neuroblastoma cells. Cancer Res. 1994;54:5414–9.

    PubMed  CAS  Google Scholar 

  133. Vaidyanathan G, Affleck DJ, Alston KL, Zhao XG, Hens M, Hunter DH, et al. A kit method for the high level synthesis of [211At]MABG. Bioorg Med Chem. 2007;15:3430–6.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

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  1. Department of Nuclear Medicine, Kanazawa University Hospital, 13-1 Takara-machi, Kanazawa, 920-8641, Japan

    Daiki Kayano & Seigo Kinuya

  2. Department of Nuclear Medicine, Fukushima Medical University Hospital, 1 Hikariga-oka, Fukushima, 960-1295, Japan

    Daiki Kayano

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Kayano, D., Kinuya, S. Current Consensus on I-131 MIBG Therapy. Nucl Med Mol Imaging 52, 254–265 (2018). https://doi.org/10.1007/s13139-018-0523-z

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