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Nuclear Medicine

MIBG in Neuroblastoma Diagnostic Imaging and Therapy

Published Online:Jan 12 2016https://doi.org/10.1148/rg.2016150099

Abstract

The authors review key clinical aspects of neuroblastoma, discuss development and use of iodine 123 (123I) metaiodobenzylguanidine (MIBG) as a diagnostic imaging agent, review 123I-MIBG scan acquisition and interpretation, and describe the rationale and necessary components for an investigational iodine 131 MIBG therapy program.

Neuroblastoma is a common malignancy observed in infants and young children. It has a varied prognosis, ranging from spontaneous regression to aggressive metastatic tumors with fatal outcomes despite multimodality therapy. Patients are divided into risk groups on the basis of age, stage, and biologic tumor factors. Multiple clinical and imaging tests are needed for accurate patient assessment. Iodine 123 (123I) metaiodobenzylguanidine (MIBG) is the first-line functional imaging agent used in neuroblastoma imaging. MIBG uptake is seen in 90% of neuroblastomas, identifying both the primary tumor and sites of metastatic disease. The addition of single photon emission computed tomography (SPECT) and SPECT/computed tomography to 123I-MIBG planar images can improve identification and characterization of sites of uptake. During scan interpretation, use of MIBG semiquantitative scoring systems improves description of disease extent and distribution and may be helpful in defining prognosis. Therapeutic use of MIBG labeled with iodine 131 (131I) is being investigated as part of research trials, both as a single agent and in conjunction with other therapies. 131I-MIBG therapy has been studied in patients with newly diagnosed neuroblastoma and those with relapsed disease. Development and implementation of an institutional 131I-MIBG therapy research program requires extensive preparation with a focus on radiation protection.

©RSNA, 2016

References

  • 1. Goodman MT, Gurney JG, Smith MA, Olshan AF. Sympathetic nervous system tumors. In: Ries LAG, Smith MA, Gurney JG, et al, eds. Cancer incidence and survival among children and adolescents: United States SEER program 1975–1995. Bethesda, Md: National Cancer Institute, SEER program. National Institutes of Health, 1999;65–72.
    Google Scholar
  • 2. Kaatsch P. Epidemiology of childhood cancer. Cancer Treat Rev 2010;36(4):277–285.
    Medline Google Scholar
  • 3. Henderson TO, Bhatia S, Pinto N, et al. Racial and ethnic disparities in risk and survival in children with neuroblastoma: a Children’s Oncology Group study. J Clin Oncol 2011;29(1):76–82.
    Medline Google Scholar
  • 4. Lonergan GJ, Schwab CM, Suarez ES, Carlson CL. Neuroblastoma, ganglioneuroblastoma, and ganglioneuroma: radiologic-pathologic correlation. RadioGraphics 2002;22(4):911–934.
    Google Scholar
  • 5. Park JR, Eggert A, Caron H. Neuroblastoma: biology, prognosis, and treatment. Hematol Oncol Clin North Am 2010;24(1):65–86.
    Medline Google Scholar
  • 6. Vo KT, Matthay KK, Neuhaus J, et al. Clinical, biologic, and prognostic differences on the basis of primary tumor site in neuroblastoma: a report from the International Neuroblastoma Risk Group project. J Clin Oncol 2014;32(28):3169–3176.
    Medline Google Scholar
  • 7. De Bernardi B, Pianca C, Pistamiglio P, et al. Neuroblastoma with symptomatic spinal cord compression at diagnosis: treatment and results with 76 cases. J Clin Oncol 2001;19(1):183–190.
    Medline Google Scholar
  • 8. Gorman MP. Update on diagnosis, treatment, and prognosis in opsoclonus-myoclonus-ataxia syndrome. Curr Opin Pediatr 2010;22(6):745–750.
    Medline Google Scholar
  • 9. Matthay KK, Blaes F, Hero B, et al. Opsoclonus myoclonus syndrome in neuroblastoma: a report from a workshop on the dancing eyes syndrome at the advances in neuroblastoma meeting in Genoa, Italy, 2004. Cancer Lett 2005;228(1-2):275–282.
    Medline Google Scholar
  • 10. DuBois SG, Kalika Y, Lukens JN, et al. Metastatic sites in stage IV and IVS neuroblastoma correlate with age, tumor biology, and survival. J Pediatr Hematol Oncol 1999;21(3):181–189.
    Medline Google Scholar
  • 11. Evans AE, Chatten J, D’Angio GJ, Gerson JM, Robinson J, Schnaufer L. A review of 17 IV-S neuroblastoma patients at the Children’s Hospital of Philadelphia. Cancer 1980;45(5):833–839.
    Medline Google Scholar
  • 12. Cohn SL, Pearson AD, London WB, et al. The International Neuroblastoma Risk Group (INRG) classification system: an INRG Task Force report. J Clin Oncol 2009;27(2):289–297.
    Medline Google Scholar
  • 13. Brodeur GM, Pritchard J, Berthold F, et al. Revisions of the international criteria for neuroblastoma diagnosis, staging, and response to treatment. J Clin Oncol 1993;11(8):1466–1477.
    Medline Google Scholar
  • 14. Monclair T, Brodeur GM, Ambros PF, et al. The International Neuroblastoma Risk Group (INRG) staging system: an INRG Task Force report. J Clin Oncol 2009;27(2):298–303.
    Medline Google Scholar
  • 15. Simon T, Hero B, Benz-Bohm G, von Schweinitz D, Berthold F. Review of image defined risk factors in localized neuroblastoma patients: results of the GPOH NB97 trial. Pediatr Blood Cancer 2008;50(5):965–969.
    Medline Google Scholar
  • 16. Brisse HJ, McCarville MB, Granata C, et al. Guidelines for imaging and staging of neuroblastic tumors: consensus report from the International Neuroblastoma Risk Group Project. Radiology 2011;261(1):243–257.
    Google Scholar
  • 17. Matthay KK, Shulkin B, Ladenstein R, et al. Criteria for evaluation of disease extent by 123I-metaiodobenzylguanidine scans in neuroblastoma: a report for the International Neuroblastoma Risk Group (INRG) Task Force. Br J Cancer 2010;102(9):1319–1326.
    Medline Google Scholar
  • 18. Vik TA, Pfluger T, Kadota R, et al. 123I-mIBG scintigraphy in patients with known or suspected neuroblastoma: results from a prospective multicenter trial. Pediatr Blood Cancer 2009;52(7):784–790.
    Medline Google Scholar
  • 19. Vallabhajosula S, Nikolopoulou A. Radioiodinated metaiodobenzylguanidine (MIBG): radiochemistry, biology, and pharmacology. Semin Nucl Med 2011;41(5):324–333.
    Medline Google Scholar
  • 20. Wieland DM, Wu J, Brown LE, Mangner TJ, Swanson DP, Beierwaltes WH. Radiolabeled adrenergic neuron-blocking agents: adrenomedullary imaging with 131I iodobenzylguanidine. J Nucl Med 1980;21(4):349–353.
    Medline Google Scholar
  • 21. Wieland DM, Brown LE, Tobes MC, et al. Imaging the primate adrenal medulla with 123I and 131I meta-iodobenzylguanidine: concise communication. J Nucl Med 1981;22(4):358–364.
    Medline Google Scholar
  • 22. Sisson JC, Frager MS, Valk TW, et al. Scintigraphic localization of pheochromocytoma. N Engl J Med 1981;305(1):12–17.
    Medline Google Scholar
  • 23. Hattner RS, Huberty JP, Engelstad BL, Gooding CA, Ablin AR. Localization of m-iodo(131I)benzylguanidine in neuroblastoma. AJR Am J Roentgenol 1984;143(2):373–374.
    Medline Google Scholar
  • 24. Kimmig B, Brandeis WE, Eisenhut M, Bubeck B, Hermann HJ, zum Winkel K. Scintigraphy of a neuroblastoma with I-131 meta-iodobenzylguanidine. J Nucl Med 1984;25(7):773–775.
    Medline Google Scholar
  • 25. Treuner J, Feine U, Niethammer D, et al. Scintigraphic imaging of neuroblastoma with [131-I]iodobenzylguanidine. Lancet 1984;1(8372):333–334.
    Medline Google Scholar
  • 26. Yanik GA, Parisi MT, Shulkin BL, et al. Semiquantitative mIBG scoring as a prognostic indicator in patients with stage 4 neuroblastoma: a report from the Children’s Oncology Group. J Nucl Med 2013;54(4):541–548.
    Medline Google Scholar
  • 27. Liu B, Zhuang H, Servaes S. Comparison of [123I]MIBG and [131I]MIBG for imaging of neuroblastoma and other neural crest tumors. Q J Nucl Med Mol Imaging 2013;57(1):21–28.
    Medline Google Scholar
  • 28. Nakajo M, Shapiro B, Copp J, 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(8):672–682.
    Medline Google Scholar
  • 29. Parisi MT, Sandler ED, Hattner RS. The biodistribution of metaiodobenzylguanidine. Semin Nucl Med 1992;22(1):46–48.
    Medline Google Scholar
  • 30. Jacobsson H, Hellström PM, Kogner P, Larsson SA. Different concentrations of I-123 MIBG and In-111 pentetreotide in the two main liver lobes in children: persisting regional functional differences after birth? Clin Nucl Med 2007;32(1):24–28.
    Medline Google Scholar
  • 31. Okuyama C, Sakane N, Yoshida T, et al. (123)I- or (125)I-metaiodobenzylguanidine visualization of brown adipose tissue. J Nucl Med 2002;43(9):1234–1240.
    Medline Google Scholar
  • 32. Okuyama C, Ushijima Y, Kubota T, et al. 123I-metaiodobenzylguanidine uptake in the nape of the neck of children: likely visualization of brown adipose tissue. J Nucl Med 2003;44(9):1421–1425.
    Medline Google Scholar
  • 33. Gelfand MJ. 123I-MIBG uptake in the neck and shoulders of a neuroblastoma patient: damage to sympathetic innervation blocks uptake in brown adipose tissue. Pediatr Radiol 2004;34(7):577–579.
    Medline Google Scholar
  • 34. Bonnin F, Lumbroso J, Tenenbaum F, Hartmann O, Parmentier C. Refining interpretation of MIBG scans in children. J Nucl Med 1994;35(5):803–810.
    Medline Google Scholar
  • 35. Paltiel HJ, Gelfand MJ, Elgazzar AH, et al. Neural crest tumors: I-123 MIBG imaging in children. Radiology 1994;190(1):117–121.
    Medline Google Scholar
  • 36. Acharya J, Chang PT, Gerard P. Abnormal MIBG uptake in a neuroblastoma patient with right upper lobe atelectasis. Pediatr Radiol 2012;42(10):1259–1262.
    Medline Google Scholar
  • 37. Schindler T, Yu C, Rossleigh M, Pereira J, Cohn R. False-positive MIBG uptake in pneumonia in a patient with stage IV neuroblastoma. Clin Nucl Med 2010;35(9):743–745.
    Medline Google Scholar
  • 38. Kulatunge CR, Son H. False-positive 123I-MIBG scintigraphy due to multiple focal nodular hyperplasia. Clin Nucl Med 2013;38(12):976–978.
    Medline Google Scholar
  • 39. Yang J, Codreanu I, Servaes S, Zhuang H. Persistent intense MIBG activity in the liver caused by prior radiation. Clin Nucl Med 2014;39(10):926–930.
    Medline Google Scholar
  • 40. Granata C, Carlini C, Conte M, Claudiani F, Campus R, Rizzo A. False positive MIBG scan due to accessory spleen. Med Pediatr Oncol 2001;37(2):138–139.
    Medline Google Scholar
  • 41. Jacobs A, Lenoir P, Delree M, Ramet J, Piepsz A. Unusual Tc-99m MDP and I-123 MIBG images in focal pyelonephritis. Clin Nucl Med 1990;15(11):821–824.
    Medline Google Scholar
  • 42. Frappaz D, Giammarile F, Thiesse P, et al. False positive MIBG scan. Med Pediatr Oncol 1997;29(6):589–592.
    Medline Google Scholar
  • 43. Rottenburger C, Juettner E, Harttrampf AC, Hentschel M, Kontny U, Roessler J. False-positive radio-iodinated metaiodobenzylguanidine (123I-MIBG) accumulation in a mast cell–infiltrated infantile haemangioma. Br J Radiol 2010;83(992):e168–e171.
    Medline Google Scholar
  • 44. Bombardieri E, Giammarile F, Aktolun C, et al. 131I/123I-metaiodobenzylguanidine (mIBG) scintigraphy: procedure guidelines for tumour imaging. Eur J Nucl Med Mol Imaging 2010;37(12):2436–2446.
    Medline Google Scholar
  • 45. Wood DE, Gilday DL, Kellan J. Stable iodine requirements for thyroid gland blockage of iodinated radiopharmaceuticals. J Can Assoc Radiol 1974;25(4):295–296.
    Medline Google Scholar
  • 46. Gelfand MJ, Parisi MT, Treves ST; Pediatric Nuclear Medicine Dose Reduction Workgroup. Pediatric radiopharmaceutical administered doses: 2010 North American consensus guidelines. J Nucl Med 2011;52(2):318–322.
    Medline Google Scholar
  • 47. Lassmann M, Biassoni L, Monsieurs M, Franzius C, Jacobs F; EANM Dosimetry and Paediatrics Committees. The new EANM paediatric dosage card. Eur J Nucl Med Mol Imaging 2008;35(9):1748.
    Medline Google Scholar
  • 48. Lassmann M, Treves ST. Pediatric radiopharmaceutical administration: harmonization of the 2007 EANM Paediatric Dosage Card (Version 1.5.2008) and the 2010 North American Consensus guideline. Eur J Nucl Med Mol Imaging 2014;41(8):1636.
    Medline Google Scholar
  • 49. Snay ER, Treves ST, Fahey FH. Improved quality of pediatric 123I-MIBG images with medium-energy collimators. J Nucl Med Technol 2011;39(2):100–104.
    Medline Google Scholar
  • 50. Gelfand MJ, Elgazzar AH, Kriss VM, Masters PR, Golsch GJ. Iodine-123–MIBG SPECT versus planar imaging in children with neural crest tumors. J Nucl Med 1994;35(11):1753–1757.
    Medline Google Scholar
  • 51. Rufini V, Fisher GA, Shulkin BL, Sisson JC, Shapiro B. Iodine-123–MIBG imaging of neuroblastoma: utility of SPECT and delayed imaging. J Nucl Med 1996;37(9):1464–1468.
    Medline Google Scholar
  • 52. Rozovsky K, Koplewitz BZ, Krausz Y, et al. Added value of SPECT/CT for correlation of MIBG scintigraphy and diagnostic CT in neuroblastoma and pheochromocytoma. AJR Am J Roentgenol 2008;190(4):1085–1090.
    Medline Google Scholar
  • 53. Fukuoka M, Taki J, Mochizuki T, Kinuya S. 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 2011;36(1):1–7.
    Medline Google Scholar
  • 54. Decarolis B, Schneider C, Hero B, et al. Iodine-123 metaiodobenzylguanidine scintigraphy scoring allows prediction of outcome in patients with stage 4 neuroblastoma: results of the Cologne interscore comparison study. J Clin Oncol 2013;31(7):944–951.
    Medline Google Scholar
  • 55. Shusterman S, Grant FD, Lorenzen W, et al. Iodine-131–labeled meta-iodobenzylguanidine therapy of children with neuroblastoma: program planning and initial experience. Semin Nucl Med 2011;41(5):354–363.
    Medline Google Scholar
  • 56. Matthay KK. Intensification of therapy using hematopoietic stem-cell support for high-risk neuroblastoma. Pediatr Transplant 1999;3(suppl 1):72–77.
    Medline Google Scholar
  • 57. Frappaz D, Michon J, Coze C, et al. LMCE3 treatment strategy: results in 99 consecutively diagnosed stage 4 neuroblastomas in children older than 1 year at diagnosis. J Clin Oncol 2000;18(3):468–476.
    Medline Google Scholar
  • 58. Stram DO, Matthay KK, O’Leary M, et al. Consolidation chemoradiotherapy and autologous bone marrow transplantation versus continued chemotherapy for metastatic neuroblastoma: a report of two concurrent Children’s Cancer Group studies. J Clin Oncol 1996;14(9):2417–2426.
    Medline Google Scholar
  • 59. Kushner BH, LaQuaglia MP, Bonilla MA, et al. Highly effective induction therapy for stage 4 neuroblastoma in children over 1 year of age. J Clin Oncol 1994;12(12):2607–2613.
    Medline Google Scholar
  • 60. Pinkerton CR, Zucker JM, Hartmann O, et al. Short duration, high dose, alternating chemotherapy in metastatic neuroblastoma. (ENSG 3C induction regimen). The European Neuroblastoma Study Group. Br J Cancer 1990;62(2):319–323.
    Medline Google Scholar
  • 61. Garaventa A, Bellagamba O, Lo Piccolo MS, et al. 131I-metaiodobenzylguanidine (131I-MIBG) therapy for residual neuroblastoma: a mono-institutional experience with 43 patients. Br J Cancer 1999;81(8):1378–1384.
    Medline Google Scholar
  • 62. Hutchinson RJ, Sisson JC, Miser JS, et al. Long-term results of 131I metaiodobenzylguanidine treatment of refractory advanced neuroblastoma. J Nucl Biol Med 1991;35(4):237–240.
    Medline Google Scholar
  • 63. Klingebiel T, Berthold F, Treuner J, et al. Metaiodobenzylguanidine (mIBG) in treatment of 47 patients with neuroblastoma: results of the German neuroblastoma trial. Med Pediatr Oncol 1991;19(2):84–88.
    Medline Google Scholar
  • 64. Matthay KK, DeSantes K, Hasegawa B, et al. Phase I dose escalation of 131I-metaiodobenzylguanidine with autologous bone marrow support in refractory neuroblastoma. J Clin Oncol 1998;16(1):229–236.
    Medline Google Scholar
  • 65. Goldberg SS, DeSantes K, Huberty JP, et al. Engraftment after myeloablative doses of 131I-metaiodobenzylguanidine followed by autologous bone marrow transplantation for treatment of refractory neuroblastoma. Med Pediatr Oncol 1998;30(6):339–346.
    Medline Google Scholar
  • 66. DuBois SG, Messina J, Maris JM, et al. Hematologic toxicity of high-dose iodine-131-metaiodobenzylguanidine therapy for advanced neuroblastoma. J Clin Oncol 2004;22(12):2452–2460.
    Medline Google Scholar
  • 67. Matthay KK, Yanik G, Messina J, 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(9):1054–1060.
    Medline Google Scholar
  • 68. de Kraker J, Hoefnagel KA, Verschuur AC, van Eck B, van Santen HM, Caron HN. Iodine-131-metaiodobenzylguanidine as initial induction therapy in stage 4 neuroblastoma patients over 1 year of age. Eur J Cancer 2008;44(4):551–556.
    Medline Google Scholar
  • 69. Klingebiel T, Feine U, Treuner J, Reuland P, Handgretinger R, Niethammer D. Treatment of neuroblastoma with 131I metaiodobenzylguanidine: long-term results in 25 patients. J Nucl Biol Med 1991;35(4):216–219.
    Medline Google Scholar
  • 70. Schmidt M, Simon T, Hero B, et al. Is there a benefit of 131I-MIBG therapy in the treatment of children with stage 4 neuroblastoma? A retrospective evaluation of the German Neuroblastoma Trial NB97 and implications for the German Neuroblastoma Trial NB2004. Nucl Med (Stuttg) 2006;45(4):145–151; quiz N39–N40.
    Google Scholar
  • 71. Wilson JS, Gains JE, Moroz V, Wheatley K, Gaze MN. A systematic review of 131I-meta iodobenzylguanidine molecular radiotherapy for neuroblastoma. Eur J Cancer 2014;50(4):801–815.
    Medline Google Scholar
  • 72. Yanik GA, Villablanca JG, Maris JM, 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(4):673–681.
    Medline Google Scholar
  • 73. French S, DuBois SG, Horn B, et al. 131I-MIBG followed by consolidation with busulfan, melphalan and autologous stem cell transplantation for refractory neuroblastoma. Pediatr Blood Cancer 2013;60(5):879–884.
    Medline Google Scholar
  • 74. DuBois SG, Matthay KK. 131I-metaiodobenzylguanidine therapy in children with advanced neuroblastoma. Q J Nucl Med Mol Imaging 2013;57(1):53–65.
    Medline Google Scholar
  • 75. Turpin BK, Morris VR, Lemen L, Weiss BD, Gelfand MJ. Minimizing nuclear medicine technologist radiation exposure during 131I-MIBG therapy. Health Phys 2013;104(2, suppl 1):S43–S46.
    Medline Google Scholar
  • 76. Wong T, Matthay KK, Boscardin WJ, Hawkins RA, Brakeman PR, DuBois SG. Acute changes in blood pressure in patients with neuroblastoma treated with 131I-metaiodobenzylguanidine (MIBG). Pediatr Blood Cancer 2013;60(9):1424–1430.
    Medline Google Scholar
  • 77. 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(11):1833–1838.
    Medline Google Scholar

Article History

Received: Apr 6 2015
Revision requested: July 15 2015
Revision received: July 23 2015
Accepted: July 24 2015
Published online: Jan 12 2016
Published in print: Jan 2016