Skip to main content
SpringerLink
Log in

Nuclear medicine and multimodality imaging of pediatric neuroblastoma

  • Review
  • Published:
Pediatric Radiology Aims and scope Submit manuscript

Abstract

Neuroblastoma is an embryonic tumor of the peripheral sympathetic nervous system and is metastatic or high risk for relapse in nearly 50% of cases. Therefore, exact staging with radiological and nuclear medicine imaging methods is crucial for defining the adequate therapeutic choice. Tumor cells express the norepinephrine transporter, which makes metaiodobenzylguanidine (MIBG), an analogue of norepinephrine, an ideal tumor specific agent for imaging. MIBG imaging has several disadvantages, such as limited spatial resolution, limited sensitivity in small lesions and the need for two or even more acquisition sessions. Most of these limitations can be overcome with positron emission tomography (PET) using [F-18]2-fluoro-2-deoxyglucose [FDG]. Furthermore, new tracers, such as fluorodopa or somatostatin receptor agonists, have been tested for imaging neuroblastoma recently. However, MIBG scintigraphy and PET alone are not sufficient for operative or biopsy planning. In this regard, a combination with morphological imaging is indispensable. This article will discuss strategies for primary and follow-up diagnosis in neuroblastoma using different nuclear medicine and radiological imaging methods as well as multimodality imaging.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Belgaumi AF, Kauffman WM, Jenkins JJ et al (1997) Blindness in children with neuroblastoma. Cancer 80:1997–2004

    Article  PubMed  CAS  Google Scholar 

  2. Kropp J, Hofmann M, Bihl H (1997) Comparison of MIBG and pentetreotide scintigraphy in children with neuroblastoma. Is the expression of somatostatin receptors a prognostic factor? Anticancer Res 17:1583–1588

    PubMed  CAS  Google Scholar 

  3. Schmidt M, Simon T, Hero B et al (2008) The prognostic impact of functional imaging with (123)I-mIBG in patients with stage 4 neuroblastoma >1 year of age on a high-risk treatment protocol: results of the German Neuroblastoma Trial NB97. Eur J Cancer 44:1552–1558

    Article  PubMed  Google Scholar 

  4. Taggart D, Dubois S, Matthay KK (2008) Radiolabeled metaiodobenzylguanidine for imaging and therapy of neuroblastoma. Q J Nucl Med Mol Imaging 52:403–418

    PubMed  CAS  Google Scholar 

  5. Custodio CM, Semelka RC, Balci NC et al (1999) Adrenal neuroblastoma in an adult with tumor thrombus in the inferior vena cava. J Magn Reson Imaging 9:621–623

    Article  PubMed  CAS  Google Scholar 

  6. DuBois SG, Matthay KK (2008) Radiolabeled metaiodobenzylguanidine for the treatment of neuroblastoma. Nucl Med Biol 35(Suppl 1):S35–48

    Article  PubMed  CAS  Google Scholar 

  7. Boubaker A, Bischof Delaloye A (2008) MIBG scintigraphy for the diagnosis and follow-up of children with neuroblastoma. Q J Nucl Med Mol Imaging 52:388–402

    PubMed  CAS  Google Scholar 

  8. Hugosson C, Nyman R, Jorulf H et al (1999) Imaging of abdominal neuroblastoma in children. Acta Radiol 40:534–542

    Article  PubMed  CAS  Google Scholar 

  9. Sofka CM, Semelka RC, Kelekis NL et al (1999) Magnetic resonance imaging of neuroblastoma using current techniques. Magn Reson Imaging 17:193–198

    Article  PubMed  CAS  Google Scholar 

  10. Taggart DR, Han MM, Quach A et al (2009) Comparison of iodine-123 metaiodobenzylguanidine (MIBG) scan and [18F]fluorodeoxyglucose positron emission tomography to evaluate response after iodine-131 MIBG therapy for relapsed neuroblastoma. J Clin Oncol 27:5343–5349

    Article  PubMed  CAS  Google Scholar 

  11. Sharp SE, Shulkin BL, Gelfand MJ et al (2009) 123I-MIBG scintigraphy and FDG PET in neuroblastoma. J Nucl Med 50:1237–1243

    Article  PubMed  Google Scholar 

  12. Mc Dowell H, Losty P, Barnes N et al (2009) Utility of FDG-PET/CT in the follow-up of neuroblastoma which became MIBG-negative. Pediatr Blood Cancer 52:552

    Article  PubMed  Google Scholar 

  13. Kleis M, Daldrup-Link H, Matthay K et al (2009) Diagnostic value of PET/CT for the staging and restaging of pediatric tumors. Eur J Nucl Med Mol Imaging 36:23–36

    Article  PubMed  Google Scholar 

  14. Shore RM (2008) Positron emission tomography/computed tomography (PET/CT) in children. Pediatr Ann 37:404–412

    Article  PubMed  Google Scholar 

  15. 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. Am J Roentgenol 190:1085–1090

    Google Scholar 

  16. Murphy JJ, Tawfeeq M, Chang B et al (2008) Early experience with PET/CT scan in the evaluation of pediatric abdominal neoplasms. J Pediatr Surg 43:2186–2192

    Article  PubMed  Google Scholar 

  17. Colavolpe C, Guedj E, Cammilleri S et al (2008) Utility of FDG-PET/CT in the follow-up of neuroblastoma which became MIBG-negative. Pediatr Blood Cancer 51:828–831

    Article  PubMed  Google Scholar 

  18. Roca I, Simo M, Sabado C et al (2007) PET/CT in paediatrics: it is time to increase its use! Eur J Nucl Med Mol Imaging 34:628–629

    Article  PubMed  Google Scholar 

  19. Franzius C, Riemann B, Vormoor J et al (2005) Metastatic neuroblastoma demonstrated by whole-body PET-CT using 11C-HED. Nuklearmedizin 44:N4–5

    PubMed  CAS  Google Scholar 

  20. Valk TW, Frager MS, Gross MD et al (1981) Spectrum of pheochromocytoma in multiple endocrine neoplasia. A scintigraphic portrayal using 131I-metaiodobenzylguanidine. Ann Intern Med 94:762–767

    PubMed  CAS  Google Scholar 

  21. Wieland DM, Brown LE, Tobes MC et al (1981) Imaging the primate adrenal medulla with [123I] and [131I] meta-iodobenzylguanidine: concise communication. J Nucl Med 22:358–364

    PubMed  CAS  Google Scholar 

  22. Sisson JC, Wieland DM (1986) Radiolabeled meta-iodobenzylguanidine: pharmacology and clinical studies. Am J Physiol Imaging 1:96–103

    PubMed  CAS  Google Scholar 

  23. Guilloteau D, Chalon S, Baulieu JL et al (1988) Comparison of MIBG and monoamines uptake mechanisms: pharmacological animal and blood platelets studies. Eur J Nucl Med 14:341–344

    Article  PubMed  CAS  Google Scholar 

  24. Claudiani F, Stimamiglio P, Bertolazzi L et al (1995) Radioiodinated meta-iodobenzylguanidine in the diagnosis of childhood neuroblastoma. Q J Nucl Med 39:21–24

    PubMed  CAS  Google Scholar 

  25. Rufini V, Calcagni ML, Baum RP (2006) Imaging of neuroendocrine tumors. Semin Nucl Med 36:228–247

    Article  PubMed  Google Scholar 

  26. Howman-Giles R, Shaw PJ, Uren RF et al (2007) Neuroblastoma and other neuroendocrine tumors. Semin Nucl Med 37:286–302

    Article  PubMed  Google Scholar 

  27. Shulkin BL, Shapiro B, Francis IR et al (1986) Primary extra-adrenal pheochromocytoma: positive I-123 MIBG imaging with negative I-131 MIBG imaging. Clin Nucl Med 11:851–854

    Article  PubMed  CAS  Google Scholar 

  28. Biasotti S, Garaventa A, Villavecchia GP et al (2000) False-negative metaiodobenzylguanidine scintigraphy at diagnosis of neuroblastoma. Med Pediatr Oncol 35:153–155

    Article  PubMed  CAS  Google Scholar 

  29. Troncone L, Rufini V, Montemaggi P et al (1990) The diagnostic and therapeutic utility of radioiodinated metaiodobenzylguanidine (MIBG). 5 years of experience. Eur J Nucl Med 16:325–335

    Article  PubMed  CAS  Google Scholar 

  30. Parisi MT, Greene MK, Dykes TM et al (1992) Efficacy of metaiodobenzylguanidine as a scintigraphic agent for the detection of neuroblastoma. Invest Radiol 27:768–773

    Article  PubMed  CAS  Google Scholar 

  31. Gelfand MJ (1993) Meta-iodobenzylguanidine in children. Semin Nucl Med 23:231–242

    Article  PubMed  CAS  Google Scholar 

  32. Hadj-Djilani NL, Lebtahi NE, Delaloye AB et al (1995) Diagnosis and follow-up of neuroblastoma by means of iodine-123 metaiodobenzylguanidine scintigraphy and bone scan, and the influence of histology. Eur J Nucl Med 22:322–329

    Article  PubMed  CAS  Google Scholar 

  33. Khafagi FA, Shapiro B, Fig LM et al (1989) Labetalol reduces iodine-131 MIBG uptake by pheochromocytoma and normal tissues. J Nucl Med 30:481–489

    PubMed  CAS  Google Scholar 

  34. Solanki KK, Bomanji J, Moyes J et al (1992) A pharmacological guide to medicines which interfere with the biodistribution of radiolabelled meta-iodobenzylguanidine (MIBG). Nucl Med Commun 13:513–521

    Article  PubMed  CAS  Google Scholar 

  35. Gordon I, Peters AM, Gutman A et al (1990) Skeletal assessment in neuroblastoma—the pitfalls of iodine-123-MIBG scans. J Nucl Med 31:129–134

    PubMed  CAS  Google Scholar 

  36. Pfluger T, Schmied C, Porn U et al (2003) Integrated imaging using MRI and 123I metaiodobenzylguanidine scintigraphy to improve sensitivity and specificity in the diagnosis of pediatric neuroblastoma. Am J Roentgenol 181:1115–1124

    Google Scholar 

  37. Geatti O, Shapiro B, Shulkin B et al (1988) Gastrointestinal iodine-131-meta-iodobenzylguanidine activity. Am J Physiol Imaging 3:188–191

    PubMed  CAS  Google Scholar 

  38. Granata C, Carlini C, Conte M et al (2001) False positive MIBG scan due to accessory spleen. Med Pediatr Oncol 37:138–139

    Article  PubMed  CAS  Google Scholar 

  39. McGarvey CK, Applegate K, Lee ND et al (2006) False-positive metaiodobenzylguanidine scan for neuroblastoma in a child with opsoclonus-myoclonus syndrome treated with adrenocorticotropic hormone (acth). J Child Neurol 21:606–610

    Article  PubMed  Google Scholar 

  40. Moralidis E, Arsos G, Papakonstantinou E et al (2008) 123I-Metaiodobenzylguanidine accumulation in a urinoma and cortex of an obstructed kidney after surgical resection of an abdominal neuroblastoma. Pediatr Radiol 38:118–121

    Article  PubMed  Google Scholar 

  41. Bahar RH, Mahmoud S, Ibrahim A et al (1988) A false positive I-131 MIBG due to dilated renal pelvis: a case report. Clin Nucl Med 13:900–902

    Article  PubMed  CAS  Google Scholar 

  42. Bonnin F, Lumbroso J, Tenenbaum F et al (1994) Refining interpretation of MIBG scans in children. J Nucl Med 35:803–810

    PubMed  CAS  Google Scholar 

  43. Matthay KK, Edeline V, Lumbroso J et al (2003) Correlation of early metastatic response by 123I-metaiodobenzylguanidine scintigraphy with overall response and event-free survival in stage IV neuroblastoma. J Clin Oncol 21:2486–2491

    Article  PubMed  Google Scholar 

  44. Matthay KK, Shulkin B, Ladenstein R et al (2010) Criteria for evaluation of disease extent by (123)I-metaiodobenzylguanidine scans in neuroblastoma: a report for the International Neuroblastoma Risk Group (INRG) Task Force. Br J Cancer 102:1319–1326

    Google Scholar 

  45. Shulkin BL, Shapiro B, Hutchinson RJ (1992) Iodine-131-metaiodobenzylguanidine and bone scintigraphy for the detection of neuroblastoma. J Nucl Med 33:1735–1740

    PubMed  CAS  Google Scholar 

  46. Daldrup-Link HE, Franzius C, Link TM et al (2001) Whole-body MR imaging for detection of bone metastases in children and young adults: comparison with skeletal scintigraphy and FDG PET. Am J Roentgenol 177:229–236

    Article  PubMed  CAS  Google Scholar 

  47. Mentzel HJ, Kentouche K, Sauner D et al (2004) Comparison of whole-body STIR-MRI and 99mTc-methylene-diphosphonate scintigraphy in children with suspected multifocal bone lesions. Eur Radiol 14:2297–2302

    Article  PubMed  Google Scholar 

  48. Goo HW, Choi SH, Ghim T et al (2005) Whole-body MRI of paediatric malignant tumours: comparison with conventional oncological imaging methods. Pediatr Radiol 35:766–773

    Article  PubMed  Google Scholar 

  49. Lebtahi N, Gudinchet F, Nenadov-Beck M et al (1997) Evaluating bone marrow metastasis of neuroblastoma with iodine-123-MIBG scintigraphy and MRI. J Nucl Med 38:1389–1392

    PubMed  CAS  Google Scholar 

  50. Kushner BH, Yeung HW, Larson SM et al (2001) Extending positron emission tomography scan utility to high-risk neuroblastoma: fluorine-18 fluorodeoxyglucose positron emission tomography as sole imaging modality in follow-up of patients. J Clin Oncol 19:3397–3405

    PubMed  CAS  Google Scholar 

  51. Shulkin BL, Hutchinson RJ, Castle VP et al (1996) Neuroblastoma: positron emission tomography with 2-[fluorine-18]-fluoro-2-deoxy-D-glucose compared with metaiodobenzylguanidine scintigraphy. Radiology 199:743–750

    PubMed  CAS  Google Scholar 

  52. Melzer HI, Coppenrath E, Schmid I et al (2011) 123I-MIBG scintigraphy/SPECT versus 18F-FDG PET in paediatric neuroblastoma. Eur J Nucl Med Mol Imaging 38:1648–1658

    Google Scholar 

  53. Rosenspire KC, Haka MS, Van Dort ME et al (1990) Synthesis and preliminary evaluation of carbon-11-meta-hydroxyephedrine: a false transmitter agent for heart neuronal imaging. J Nucl Med 31:1328–1334

    PubMed  CAS  Google Scholar 

  54. Shulkin BL, Wieland DM, Baro ME et al (1996) PET hydroxyephedrine imaging of neuroblastoma. J Nucl Med 37:16–21

    PubMed  CAS  Google Scholar 

  55. Schwaiger M, Hutchins GD, Kalff V et al (1991) Evidence for regional catecholamine uptake and storage sites in the transplanted human heart by positron emission tomography. J Clin Invest 87:1681–1690

    Article  PubMed  CAS  Google Scholar 

  56. Schwaiger M, Kalff V, Rosenspire K et al (1990) Noninvasive evaluation of sympathetic nervous system in human heart by positron emission tomography. Circulation 82:457–464

    Article  PubMed  CAS  Google Scholar 

  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

    PubMed  CAS  Google Scholar 

  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

    PubMed  Google Scholar 

  59. Becherer A, Szabo M, Karanikas G et al (2004) Imaging of advanced neuroendocrine tumors with (18)F-FDOPA PET. J Nucl Med 45:1161–1167

    PubMed  CAS  Google Scholar 

  60. Hoegerle S, Nitzsche E, Altehoefer C et al (2002) Pheochromocytomas: detection with 18F DOPA whole body PET—initial results. Radiology 222:507–512

    Article  PubMed  Google Scholar 

  61. Mamede M, Carrasquillo JA, Chen CC et al (2006) Discordant localization of 2-[18F]-fluoro-2-deoxy-D-glucose in 6-[18F]-fluorodopamine- and [(123)I]-metaiodobenzylguanidine-negative metastatic pheochromocytoma sites. Nucl Med Commun 27:31–36

    Article  PubMed  Google Scholar 

  62. Piccardo A, Lopci E, Conte M et al (2012) Comparison of 18F-dopa PET/CT and 123I-MIBG scintigraphy in stage 3 and 4 neuroblastoma: a pilot study. Eur J Nucl Med Mol Imaging 39:57–71

    Google Scholar 

  63. O’Dorisio MS, Chen F, O’Dorisio TM et al (1994) Characterization of somatostatin receptors on human neuroblastoma tumors. Cell Growth Differ 5:1–8

    PubMed  Google Scholar 

  64. Albers AR, O’Dorisio MS, Balster DA et al (2000) Somatostatin receptor gene expression in neuroblastoma. Regul Pept 88:61–73

    Article  PubMed  CAS  Google Scholar 

  65. Georgantzi K, Tsolakis AV, Stridsberg M et al (2011) Differentiated expression of somatostatin receptor subtypes in experimental models and clinical neuroblastoma. Pediatr Blood Cancer 56:584–589

    Google Scholar 

  66. Gains JE, Bomanji JB, Fersht NL et al (2011) 177Lu-DOTATATE molecular radiotherapy for childhood neuroblastoma. J Nucl Med 52:1041–1047

    Google Scholar 

  67. Muller MF, Krestin GP, Willi UV (1993) Abdominal tumors in children. A comparison between magnetic resonance tomography (MRT) and ultrasonography (US). Rofo 158:9–14

    Article  PubMed  CAS  Google Scholar 

  68. Daldrup HE, Link TM, Wortler K et al (1998) MR imaging of thoracic tumors in pediatric patients. Am J Roentgenol 170:1639–1644

    Article  PubMed  CAS  Google Scholar 

  69. Kaste SC (2004) Issues specific to implementing PET-CT for pediatric oncology: what we have learned along the way. Pediatr Radiol 34:205–213

    Article  PubMed  Google Scholar 

  70. Bar-Sever Z, Keidar Z, Ben-Barak A et al (2007) The incremental value of FDG PET/CT in paediatric malignancies. Eur J Nucl Med Mol Imaging 34:630–637

    Article  PubMed  Google Scholar 

  71. Olson PN, Everson LI, Griffiths HJ (1994) Staging of musculoskeletal tumors. Radiol Clin N Am 32:151–162

    PubMed  CAS  Google Scholar 

  72. Silberstein EB, Saenger EL, Tofe AJ et al (1973) Imaging of bone metastases with 99m Tc-Sn-EHDP (diphosphonate), 18F, and skeletal radiography. A comparison of sensitivity. Radiology 107:551–555

    PubMed  CAS  Google Scholar 

  73. Hahn K, Charron M, Shulkin BL (2003) Role of MR imaging and iodine 123 MIBG scintigraphy in staging of pediatric neuroblastoma. Radiology 227:908, author reply 908–909

    Article  PubMed  Google Scholar 

  74. Shah Syed GM, Naseer H, Usmani GN et al (2004) Role of iodine-131 MIBG scanning in the management of paediatric patients with neuroblastoma. Med Princ Pract 13:196–200

    Article  PubMed  CAS  Google Scholar 

  75. Moon L, McHugh K (2005) Advances in paediatric tumour imaging. Arch Dis Child 90:608–611

    Article  PubMed  CAS  Google Scholar 

  76. Nanni C, Rubello D, Castellucci P et al (2006) FDG PET/CT fusion imaging in paediatric solid extracranial tumours. Biomed Pharmacother 60:593–606

    Article  PubMed  CAS  Google Scholar 

  77. Yeung HW, Schoder H, Smith A et al (2005) Clinical value of combined positron emission tomography/computed tomography imaging in the interpretation of 2-deoxy-2-[F-18]fluoro-D-glucose-positron emission tomography studies in cancer patients. Mol Imaging Biol 7:229–235

    Article  PubMed  Google Scholar 

  78. Franzius C, Daldrup-Link HE, Sciuk J et al (2001) FDG-PET for detection of pulmonary metastases from malignant primary bone tumors: comparison with spiral CT. Ann Oncol 12:479–486

    Article  PubMed  CAS  Google Scholar 

  79. Volker T, Denecke T, Steffen I et al (2007) Positron emission tomography for staging of pediatric sarcoma patients: results of a prospective multicenter trial. J Clin Oncol 25:5435–5441

    Article  PubMed  Google Scholar 

  80. Gerth HU, Juergens KU, Dirksen U et al (2007) Significant benefit of multimodal imaging: PET/CT compared with PET alone in staging and follow-up of patients with Ewing tumors. J Nucl Med 48:1932–1939

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Nuclear Medicine, Ludwig-Maximilians-University of Munich, Ziemssenstr. 1, 80336, Munich, Germany

    Wolfgang Peter Mueller & Thomas Pfluger

  2. Department of Radiology, Ludwig-Maximilians-University of Munich, Ziemssenstr. 1, 80336, Munich, Germany

    Eva Coppenrath

Authors
  1. Wolfgang Peter Mueller
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Eva Coppenrath
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Thomas Pfluger
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Wolfgang Peter Mueller.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Mueller, W.P., Coppenrath, E. & Pfluger, T. Nuclear medicine and multimodality imaging of pediatric neuroblastoma. Pediatr Radiol 43, 418–427 (2013). https://doi.org/10.1007/s00247-012-2512-1

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00247-012-2512-1

Keywords

Search

Navigation