Abstract
Nuclear medicine has a central role in the diagnosis, staging, response assessment and long-term follow-up of neuroblastoma, the most common solid extracranial tumour in children. These EANM guidelines include updated information on 123I-mIBG, the most common study in nuclear medicine for the evaluation of neuroblastoma, and on PET/CT imaging with 18F-FDG, 18F-DOPA and 68Ga-DOTA peptides. These PET/CT studies are increasingly employed in clinical practice. Indications, advantages and limitations are presented along with recommendations on study protocols, interpretation of findings and reporting results.
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References
Wilson LM, Draper GJ. Neuroblastoma, its natural history and prognosis: a study of 487 cases. Br Med J. 1974;3:301–7.
Young J, Ries L, Silverberg E, Horm J, Miller R. Cancer incidence, survival, and mortality for children younger than age 15 years. Cancer. 1986;58:598–602.
Cistaro A, Quartuccio N, Caobelli F, Piccardo A, Paratore R, Coppolino P, et al. 124I-MIBG: a new promising positron-emitting radiopharmaceutical for the evaluation of neuroblastoma. Nucl Med Rev Cent East Eur. 2015;18:102–6.
Huang SY, Bolch WE, Lee C, Van Brocklin HF, Pampaloni MH, Hawkins RA, et al. Patient-specific dosimetry using pretherapy [124I]m-iodobenzylguanidine ([124I]mIBG) dynamic PET/CT imaging before [131I]mIBG targeted radionuclide therapy for neuroblastoma. Mol Imaging Biol. 2015;17:284–94.
Hartung-Knemeyer V, Rosenbaum-Krumme S, Buchbender C, Poppel T, Brandau W, Jentzen W, et al. Malignant pheochromocytoma imaging with [124I]mIBG PET/MR. J Clin Endocrinol Metab. 2012;97:3833–4.
Lee CL, Wahnishe H, Sayre GA, Cho HM, Kim HJ, Hernandez-Pampaloni M, et al. Radiation dose estimation using preclinical imaging with I124-metaiodobenzylguanidine (MIBG) PET. Med Phys. 2010;37:4861–7.
Beijst C, de Keizer B, Lam M, Janssens GO, Tytgat GAM, de Jong H. A phantom study: should 124 I-mIBG PET/CT replace 123 I-mIBG SPECT/CT? Med Phys. 2017;44:1624–31.
Suh M, Park HJ, Choi HS, So Y, Lee BC, Lee WW. Case report of PET/CT imaging of a patient with neuroblastoma using 18F-FPBG. Pediatrics. 2014;134:e1731–4.
Zhang H, Huang R, Cheung NK, Guo H, Zanzonico PB, Thaler HT, et al. Imaging the norepinephrine transporter in neuroblastoma: a comparison of [18F]-MFBG and 123I-MIBG. Clin Cancer Res. 2014;20:2182–91.
Pandit-Taskar N, Zanzonico P, Staton KD, Carrasquillo JA, Reidy-Lagunes D, Lyashchenko S, et al. Biodistribution and dosimetry of (18)F-meta-fluorobenzylguanidine: a first-in-human PET/CT imaging study of patients with neuroendocrine malignancies. J Nucl Med. 2018;59:147–53.
Pepe G, Bombardieri E, Lorenzoni A, Chiti A. Single-photon emission computed tomography tracers in the diagnostics of neuroendocrine tumors. PET Clin. 2014;9:11–26.
Nadel HR. SPECT/CT in pediatric patient management. Eur J Nucl Med Mol Imaging. 2014;41(Suppl 1):S104–14.
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;36:1–7.
Rozovsky K, Koplewitz BZ, Krausz Y, Revel-Vilk S, Weintraub M, Chisin R, et al. Added value of SPECT/CT for correlation of MIBG scintigraphy and diagnostic CT in neuroblastoma and pheochromocytoma. AJR Am J Roentgenol. 2008;190:1085–90.
Hicks RJ, Hofman MS. Is there still a role for SPECT-CT in oncology in the PET-CT era? Nat Rev Clin Oncol. 2012;9:712–20.
Piccardo A, Lopci E, Conte M, Garaventa A, Foppiani L, Altrinetti V, et al. 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. 2012;39:57–71.
Kroiss A, Putzer D, Uprimny C, Decristoforo C, Gabriel M, Santner W, et al. Functional imaging in phaeochromocytoma and neuroblastoma with 68Ga-DOTA-Tyr 3-octreotide positron emission tomography and 123I-metaiodobenzylguanidine. Eur J Nucl Med Mol Imaging. 2011;38:865–73.
Biermann M, Schwarzlmuller T, Fasmer KE, Reitan BC, Johnsen B, Rosendahl K. Is there a role for PET-CT and SPECT-CT in pediatric oncology? Acta Radiol. 2013;54:1037–45.
Bleeker G, Tytgat GA, Adam JA, Caron HN, Kremer LC, Hooft L, et al. 123I-MIBG scintigraphy and 18F-FDG-PET imaging for diagnosing neuroblastoma. Cochrane Database Syst Rev. 2015;(9):CD009263.
Jacobson AF, Deng H, Lombard J, Lessig HJ, Black RR. 123I-meta-iodobenzylguanidine scintigraphy for the detection of neuroblastoma and pheochromocytoma: results of a meta-analysis. J Clin Endocrinol Metab. 2010;95:2596–606.
Shulkin BL, Wieland DM, Baro ME, Ungar DR, Mitchell DS, Dole MG, et al. PET hydroxyephedrine imaging of neuroblastoma. J Nucl Med. 1996;37:16–21.
Ambrosini V, Morigi JJ, Nanni C, Castellucci P, Fanti S. Current status of PET imaging of neuroendocrine tumours ([18F]FDOPA, [68Ga]tracers, [11C]/[18F]-HTP). Q J Nucl Med Mol Imaging. 2015;59:58–69.
Leung A, Shapiro B, Hattner R, Kim E, de Kraker J, Ghazzar N, et al. Specificity of radioiodinated MIBG for neural crest tumors in childhood. J Nucl Med. 1997;38:1352–7.
Shulkin BL, Shapiro B. Current concepts on the diagnostic use of MIBG in children. J Nucl Med. 1998;39:679–88.
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.
Vik TA, Pfluger T, Kadota R, Castel V, Tulchinsky M, Farto JC, et al. (123)I-mIBG scintigraphy in patients with known or suspected neuroblastoma: results from a prospective multicenter trial. Pediatr Blood Cancer. 2009;52:784–90.
Matthay KK, Shulkin B, Ladenstein R, Michon J, Giammarile F, Lewington V, et al. 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. 2010;102:1319–26.
Taggart DR, Han MM, Quach A, Groshen S, Ye W, Villablanca JG, et al. 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. 2009;27:5343–9.
Sharp SE, Shulkin BL, Gelfand MJ, Salisbury S, Furman WL. 123I-MIBG scintigraphy and 18F-FDG PET in neuroblastoma. J Nucl Med. 2009;50:1237–43.
Suc A, Lumbroso J, Rubie H, Hattchouel JM, Boneu A, Rodary C, et al. Metastatic neuroblastoma in children older than one year: prognostic significance of the initial metaiodobenzylguanidine scan and proposal for a scoring system. Cancer. 1996;77:805–11.
Schmidt M, Simon T, Hero B, Schicha H, Berthold F. 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. 2008;44:1552–8.
Ladenstein R, Philip T, Lasset C, Hartmann O, Garaventa A, Pinkerton R, et al. Multivariate analysis of risk factors in stage 4 neuroblastoma patients over the age of one year treated with megatherapy and stem-cell transplantation: a report from the European Bone Marrow Transplantation Solid Tumor Registry. J Clin Oncol. 1998;16:953–65.
Lewington V, Lambert B, Poetschger U, Sever ZB, Giammarile F, McEwan AJ, et al. 123I-mIBG scintigraphy in neuroblastoma: development of a SIOPEN semi-quantitative reporting method by an international panel. Eur J Nucl Med Mol Imaging. 2017;44:234–41.
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;57:21–8.
Sharp SE, Trout AT, Weiss BD, Gelfand MJ. MIBG in neuroblastoma diagnostic imaging and therapy. Radiographics. 2016;36:258–78.
Bombardieri E, Giammarile F, Aktolun C, Baum RP, Bischof Delaloye A, Maffioli L, et al. 131I/123I-metaiodobenzylguanidine (mIBG) scintigraphy: procedure guidelines for tumour imaging. Eur J Nucl Med Mol Imaging. 2010;37:2436–46.
Olivier P, Colarinha P, Fettich J, Fischer S, Frokier J, Giammarile F, et al. Guidelines for radioiodinated MIBG scintigraphy in children. Eur J Nucl Med Mol Imaging. 2003;30:B45–50.
Vallabhajosula S, Nikolopoulou A. Radioiodinated metaiodobenzylguanidine (MIBG): radiochemistry, biology, and pharmacology. Semin Nucl Med. 2011;41:324–33.
Streby KA, Shah N, Ranalli MA, Kunkler A, Cripe TP. Nothing but NET: a review of norepinephrine transporter expression and efficacy of 131I-mIBG therapy. Pediatr Blood Cancer. 2015;62:5–11.
Von Moll L, McEwan AJ, Shapiro B, Sisson JC, Gross MD, Lloyd R, et al. Iodine-131 MIBG scintigraphy of neuroendocrine tumors other than pheochromocytoma and neuroblastoma. J Nucl Med. 1987;28:979–88.
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.
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.
Shapiro B, Copp JE, Sisson JC, Eyre PL, Wallis J, Beierwaltes WH. Iodine-131 metaiodobenzylguanidine for the locating of suspected pheochromocytoma: experience in 400 cases. J Nucl Med. 1985;26:576–85.
Khafagi FA, Shapiro B, Fischer M, Sisson JC, Hutchinson R, Beierwaltes WH. Phaeochromocytoma and functioning paraganglioma in childhood and adolescence: role of iodine 131 metaiodobenzylguanidine. Eur J Nucl Med. 1991;18:191–8.
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.
Jacobsson H, Hellstrom 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;32:24–8.
Parisi MT, Sandler ED, Hattner RS. The biodistribution of metaiodobenzylguanidine. Semin Nucl Med. 1992;22:46–8.
Bomanji J, Britton KE. Uterine uptake of iodine-123 metaiodobenzylguanidine during the menstrual phase of uterine cycle. Clin Nucl Med. 1987;12:601–3.
Okuyama C, Ushijima Y, Kubota T, Yoshida T, Nakai T, Kobayashi K, et al. 123I-Metaiodobenzylguanidine uptake in the nape of the neck of children: likely visualization of brown adipose tissue. J Nucl Med. 2003;44:1421–5.
Farahati J, Bier D, Scheubeck M, Lassmann M, Schelper LF, Grelle I, et al. Effect of specific activity on cardiac uptake of iodine-123-MIBG. J Nucl Med. 1997;38:447–51.
Bonnin F, Lumbroso J, Tenenbaum F, Hartmann O, Parmentier C. Refining interpretation of MIBG scans in children. J Nucl Med. 1994;35:803–10.
Dwamena BA, Zempel S, Klopper JF, Van Heerden B, Wieland D, Shapiro B. Brain uptake of iodine-131 metaiodobenzylguanidine following therapy of malignant pheochromocytoma. Clin Nucl Med. 1998;23:441–5.
Mangner TJ, Tobes MC, Wieland DW, Sisson JC, Shapiro B. Metabolism of iodine-131 metaiodobenzylguanidine in patients with metastatic pheochromocytoma. J Nucl Med. 1986;27:37–44.
Jacobson AF, Travin MI. Impact of medications on mIBG uptake, with specific attention to the heart: comprehensive review of the literature. J Nucl Cardiol. 2015;22:980–93.
Khafagi FA, Shapiro B, Fig LM, Mallette S, Sisson JC. Labetalol reduces iodine-131 MIBG uptake by pheochromocytoma and normal tissues. J Nucl Med. 1989;30:481–9.
Wood DE, Gilday DL, Kellan J. Stable iodine requirements for thyroid gland blockage of iodinated radiopharmaceuticals. J Can Assoc Radiol. 1974;25:295–6.
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;52:318–22.
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;35:1748.
Lassmann M, Treves ST; EANM/SNMMI Paediatric Dosage Harmonization Working Group. Paediatric radiopharmaceutical administration: harmonization of the 2007 EANM paediatric dosage card (version 1.5.2008) and the 2010 North American consensus guidelines. Eur J Nucl Med Mol Imaging. 2014;41:1036–41.
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;41:1636.
Treves ST, Lassmann M. International guidelines for pediatric radiopharmaceutical administered activities. J Nucl Med. 2014;55:869–70.
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;37:1464–8.
Snay ER, Treves ST, Fahey FH. Improved quality of pediatric 123I-MIBG images with medium-energy collimators. J Nucl Med Technol. 2011;39:100–4.
Liu B, Servaes S, Zhuang H. SPECT/CT MIBG imaging is crucial in the follow-up of the patients with high-risk neuroblastoma. Clin Nucl Med. 2018;43:232–8.
Gelfand MJ. Dose reduction in pediatric hybrid and planar imaging. Q J Nucl Med Mol Imaging. 2010;54:379–88.
Gelfand MJ, Lemen LC. PET/CT and SPECT/CT dosimetry in children: the challenge to the pediatric imager. Semin Nucl Med. 2007;37:391–8.
Pfluger T, Schmied C, Porn U, Leinsinger G, Vollmar C, Dresel S, et al. Integrated imaging using MRI and 123I metaiodobenzylguanidine scintigraphy to improve sensitivity and specificity in the diagnosis of pediatric neuroblastoma. AJR Am J Roentgenol. 2003;181:1115–24.
Melzer HI, Coppenrath E, Schmid I, Albert MH, von Schweinitz D, Tudball C, et al. 123I-MIBG scintigraphy/SPECT versus 18F-FDG PET in paediatric neuroblastoma. Eur J Nucl Med Mol Imaging. 2011;38:1648–58.
Piccardo A, Puntoni M, Lopci E, Conte M, Foppiani L, Sorrentino S, et al. Prognostic value of 18F-DOPA PET/CT at the time of recurrence in patients affected by neuroblastoma. Eur J Nucl Med Mol Imaging. 2014;41:1046–56.
Piccardo A, Lopci E, Conte M, Cabria M, Cistaro A, Garaventa A, et al. Bone and lymph node metastases from neuroblastoma detected by 18F-DOPA-PET/CT and confirmed by posttherapy 131I-MIBG but negative on diagnostic 123I-MIBG scan. Clin Nucl Med. 2014;39:e80–3.
Piccardo A, Lopci E, Conte M, Foppiani L, Garaventa A, Cabria M, et al. PET/CT imaging in neuroblastoma. Q J Nucl Med Mol Imaging. 2013;57:29–39.
Acharya J, Chang PT, Gerard P. Abnormal MIBG uptake in a neuroblastoma patient with right upper lobe atelectasis. Pediatr Radiol. 2012;42:1259–62.
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;35:743–5.
Kulatunge CR, Son H. False-positive 123I-MIBG scintigraphy due to multiple focal nodular hyperplasia. Clin Nucl Med. 2013;38:976–8.
Yang J, Codreanu I, Servaes S, Zhuang H. Persistent intense MIBG activity in the liver caused by prior radiation. Clin Nucl Med. 2014;39:926–30.
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;15:821–4.
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:e168–71.
Frappaz D, Giammarile F, Thiesse P, Ranchere-Vince D, Louis D, Guibaud L, et al. False positive MIBG scan. Med Pediatr Oncol. 1997;29:589–92.
Granata C, Carlini C, Conte M, Claudiani F, Campus R, Rizzo A. False positive MIBG scan due to accessory spleen. Med Pediatr Oncol. 2001;37:138–9.
Mueller WP, Coppenrath E, Pfluger T. Nuclear medicine and multimodality imaging of pediatric neuroblastoma. Pediatr Radiol. 2013;43:418–27.
Biasotti S, Garaventa A, Villavecchia GP, Cabria M, Nantron M, De Bernardi B. False-negative metaiodobenzylguanidine scintigraphy at diagnosis of neuroblastoma. Med Pediatr Oncol. 2000;35:153–5.
Matthay KK, Brisse H, Couanet D, Couturier J, Benard J, Mosseri V, et al. Central nervous system metastases in neuroblastoma: radiologic, clinical, and biologic features in 23 patients. Cancer. 2003;98:155–65.
Matthay KK, Edeline V, Lumbroso J, Tanguy ML, Asselain B, Zucker JM, et al. Correlation of early metastatic response by 123I-metaiodobenzylguanidine scintigraphy with overall response and event-free survival in stage IV neuroblastoma. J Clin Oncol. 2003;21:2486–91.
Katzenstein HM, Cohn SL, Shore RM, Bardo DM, Haut PR, Olszewski M, et al. Scintigraphic response by 123I-metaiodobenzylguanidine scan correlates with event-free survival in high-risk neuroblastoma. J Clin Oncol. 2004;22:3909–15.
Ady N, Zucker JM, Asselain B, Edeline V, Bonnin F, Michon J, et al. A new 123I-MIBG whole body scan scoring method – application to the prediction of the response of metastases to induction chemotherapy in stage IV neuroblastoma. Eur J Cancer. 1995;31A:256–61.
Yanik GA, Parisi MT, Shulkin BL, Naranjo A, Kreissman SG, London WB, 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;54:541–8.
Shulkin BL, Shapiro B, Hutchinson RJ. Iodine-131-metaiodobenzylguanidine and bone scintigraphy for the detection of neuroblastoma. J Nucl Med. 1992;33:1735–40.
Boubaker A, Bischof Delaloye A. MIBG scintigraphy for the diagnosis and follow-up of children with neuroblastoma. Q J Nucl Med Mol Imaging. 2008;52:388–402.
Kushner BH, Yeh SD, Kramer K, Larson SM, Cheung NK. Impact of metaiodobenzylguanidine scintigraphy on assessing response of high-risk neuroblastoma to dose-intensive induction chemotherapy. J Clin Oncol. 2003;21:1082–6.
Cheung NK, Kushner BH. Should we replace bone scintigraphy plus CT with MR imaging for staging of neuroblastoma? Radiology. 2003;226:286–7. Author reply 287–8.
Brisse HJ, McCarville MB, Granata C, Krug KB, Wootton-Gorges SL, Kanegawa K, et al. Guidelines for imaging and staging of neuroblastic tumors: consensus report from the International Neuroblastoma Risk Group Project. Radiology. 2011;261:243–57.
Stauss J, Hahn K, Mann M, De Palma D. Guidelines for paediatric bone scanning with 99mTc-labelled radiopharmaceuticals and 18F-fluoride. Eur J Nucl Med Mol Imaging. 2010;37:1621–8.
Boellaard R, Delgado-Bolton R, Oyen WJ, Giammarile F, Tatsch K, Eschner W, et al. FDG PET/CT: EANM procedure guidelines for tumour imaging: version 2.0. Eur J Nucl Med Mol Imaging. 2015;42:328–54.
Shulkin BL, Hutchinson RJ, Castle VP, Yanik GA, Shapiro B, Sisson JC. Neuroblastoma: positron emission tomography with 2-[fluorine-18]-fluoro-2-deoxy-D-glucose compared with metaiodobenzylguanidine scintigraphy. Radiology. 1996;199:743–50.
Li C, Zhang J, Chen S, Huang S, Wu S, Zhang L, et al. Prognostic value of metabolic indices and bone marrow uptake pattern on preoperative 18F-FDG PET/CT in pediatric patients with neuroblastoma. Eur J Nucl Med Mol Imaging. 2018;45:306–15.
Sharp SE, Gelfand MJ, Absalon MJ. Altered FDG uptake patterns in pediatric lymphoblastic lymphoma patients receiving induction chemotherapy that includes very high dose corticosteroids. Pediatr Radiol. 2012;42:331–6.
Zukotynski KA, Fahey FH, Laffin S, Davis R, Treves ST, Grant FD, et al. Constant ambient temperature of 24 degrees C significantly reduces FDG uptake by brown adipose tissue in children scanned during the winter. Eur J Nucl Med Mol Imaging. 2009;36:602–6.
Gelfand MJ, O'Hara SM, Curtwright LA, Maclean JR. Pre-medication to block [18F]FDG uptake in the brown adipose tissue of pediatric and adolescent patients. Pediatr Radiol. 2005;35:984–90.
Parysow O, Mollerach AM, Jager V, Racioppi S, San Roman J, Gerbaudo VH. Low-dose oral propranolol could reduce brown adipose tissue F-18 FDG uptake in patients undergoing PET scans. Clin Nucl Med. 2007;32:351–7.
Alessio AM, Kinahan PE, Manchanda V, Ghioni V, Aldape L, Parisi MT. Weight-based, low-dose pediatric whole-body PET/CT protocols. J Nucl Med. 2009;50:1570–7.
Brady SL, Shulkin BL. Ultralow dose computed tomography attenuation correction for pediatric PET CT using adaptive statistical iterative reconstruction. Med Phys. 2015;42:558–66.
Nadel HR, Shulkin B. Pediatric positron emission tomography-computed tomography protocol considerations. Semin Ultrasound CT MR. 2008;29:271–6.
Shammas A, Lim R, Charron M. Pediatric FDG PET/CT: physiologic uptake, normal variants, and benign conditions. Radiographics. 2009;29:1467–86.
Papathanasiou ND, Gaze MN, Sullivan K, Aldridge M, Waddington W, Almuhaideb A, et al. 18F-FDG PET/CT and 123I-metaiodobenzylguanidine imaging in high-risk neuroblastoma: diagnostic comparison and survival analysis. J Nucl Med. 2011;52:519–25.
Colavolpe C, Guedj E, Cammilleri S, Taieb D, Mundler O, Coze C. Utility of FDG-PET/CT in the follow-up of neuroblastoma which became MIBG-negative. Pediatr Blood Cancer. 2008;51:828–31.
McDowell H, Losty P, Barnes N, Kokai G. Utility of FDG-PET/CT in the follow-up of neuroblastoma which became MIBG-negative. Pediatr Blood Cancer. 2009;52:552.
Jager PL, Chirakal R, Marriott CJ, Brouwers AH, Koopmans KP, Gulenchyn KY. 6-L-18F-fluorodihydroxyphenylalanine PET in neuroendocrine tumors: basic aspects and emerging clinical applications. J Nucl Med. 2008;49:573–86.
Fottner C, Helisch A, Anlauf M, Rossmann H, Musholt TJ, Kreft A, et al. 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. 2010;95:2800–10.
LaBrosse E, Comoy E, Bohuon C, Zucker J, Schweisguth O. Catecholamine metabolism in neuroblastoma. J Natl Cancer Inst. 1976;57:633–8.
Brodeur G. Neuroblastoma and other peripheral neuroectodermal tumors. In: Fernbach D, Vietti T, editors. Clinical pediatric oncology. St. Louis: CV Mosby; 1991. p. 337.
Timmers HJ, Chen CC, Carrasquillo JA, Whatley M, Ling A, Havekes B, et al. Comparison of 18F-fluoro-L-DOPA, 18F-fluoro-deoxyglucose, and 18F-fluorodopamine PET and 123I-MIBG scintigraphy in the localization of pheochromocytoma and paraganglioma. J Clin Endocrinol Metab. 2009;94:4757–67.
Kauhanen S, Seppanen M, Ovaska J, Minn H, Bergman J, Korsoff P, et al. The clinical value of [18F]fluoro-dihydroxyphenylalanine positron emission tomography in primary diagnosis, staging, and restaging of neuroendocrine tumors. Endocr Relat Cancer. 2009;16:255–65.
Lopci E, Piccardo A, Nanni C, Altrinetti V, Garaventa A, Pession A, et al. 18F-DOPA PET/CT in neuroblastoma: comparison of conventional imaging with CT/MR. Clin Nucl Med. 2012;37:e73–8.
Lu MY, Liu YL, Chang HH, Jou ST, Yang YL, Lin KH, et al. Characterization of neuroblastic tumors using 18F-FDOPA PET. J Nucl Med. 2013;54:42–9.
Brown WD, Oakes TR, DeJesus OT, Taylor MD, Roberts AD, Nickles RJ, et al. Fluorine-18-fluoro-L-DOPA dosimetry with carbidopa pretreatment. J Nucl Med. 1998;39:1884–91.
Paterson A, Frush DP, Donnelly LF. Helical CT of the body: are settings adjusted for pediatric patients? AJR Am J Roentgenol. 2001;176:297–301.
Arch ME, Frush DP. Pediatric body MDCT: a 5-year follow-up survey of scanning parameters used by pediatric radiologists. AJR Am J Roentgenol. 2008;191:611–7.
Chondrogiannis S, Grassetto G, Marzola MC, Rampin L, Massaro A, Bellan E, et al. 18F-DOPA PET/CT biodistribution consideration in 107 consecutive patients with neuroendocrine tumours. Nucl Med Commun. 2012;33:179–84.
Lopci E, D'Ambrosio D, Nanni C, Chiti A, Pession A, Marengo M, et al. Feasibility of carbidopa premedication in pediatric patients: a pilot study. Cancer Biother Radiopharm. 2012;27:729–33.
O'Dorisio MS, Chen F, O'Dorisio TM, Wray D, Qualman SJ. Characterization of somatostatin receptors on human neuroblastoma tumors. Cell Growth Differ. 1994;5:1–8.
Albers AR, O'Dorisio MS, Balster DA, Caprara M, Gosh P, Chen F, et al. Somatostatin receptor gene expression in neuroblastoma. Regul Pept. 2000;88:61–73.
Moertel CL, Reubi JC, Scheithauer BS, Schaid DJ, Kvols LK. Expression of somatostatin receptors in childhood neuroblastoma. Am J Clin Pathol. 1994;102:752–6.
Georgantzi K, Tsolakis AV, Stridsberg M, Jakobson A, Christofferson R, Janson ET. Differentiated expression of somatostatin receptor subtypes in experimental models and clinical neuroblastoma. Pediatr Blood Cancer. 2011;56:584–9.
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.
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;52:1041–7.
Hofman MS, Lau WF, Hicks RJ. Somatostatin receptor imaging with 68Ga DOTATATE PET/CT: clinical utility, normal patterns, pearls, and pitfalls in interpretation. Radiographics. 2015;35:500–16.
Walker RC, Smith GT, Liu E, Moore B, Clanton J, Stabin M. Measured human dosimetry of 68Ga-DOTATATE. J Nucl Med. 2013;54:855–60.
Sandstrom M, Velikyan I, Garske-Roman U, Sorensen J, Eriksson B, Granberg D, et al. Comparative biodistribution and radiation dosimetry of 68Ga-DOTATOC and 68Ga-DOTATATE in patients with neuroendocrine tumors. J Nucl Med. 2013;54:1755–9.
Hartmann H, Freudenberg R, Oehme L, Zophel K, Schottelius M, Wester HJ, et al. Dosimetric measurements of (68)Ga-high affinity DOTATATE: twins in spirit – part III. Nuklearmedizin. 2014;53:211–6.
Virgolini I, Ambrosini V, Bomanji JB, Baum RP, Fanti S, Gabriel M, et al. Procedure guidelines for PET/CT tumour imaging with 68Ga-DOTA-conjugated peptides: 68Ga-DOTA-TOC, 68Ga-DOTA-NOC, 68Ga-DOTA-TATE. Eur J Nucl Med Mol Imaging. 2010;37:2004–10.
EANM. Dosage Calculator.
Machado JS, Beykan S, Herrmann K, Lassmann M. Recommended administered activities for (68)Ga-labelled peptides in paediatric nuclear medicine. Eur J Nucl Med Mol Imaging. 2016;43:2036–9.
Solanki KK, Bomanji J, Moyes J, Mather SJ, Trainer PJ, Britton KE. A pharmacological guide to medicines which interfere with the biodistribution of radiolabelled meta-iodobenzylguanidine (MIBG). Nucl Med Commun. 1992;13:513–21.
Stefanelli A, Treglia G, Bruno I, Rufini V, Giordano A. Pharmacological interference with 123I-metaiodobenzylguanidine: a limitation to developing cardiac innervation imaging in clinical practice? Eur Rev Med Pharmacol Sci. 2013;17:1326–33.
Acknowledgments
These guidelines summarize the views of leading experts from the EANM and other continents and reflect recommendations for which the EANM cannot be held responsible. The recommendations should be considered in the context of good nuclear medicine practice and are not a substitute for national and international legal or regulatory provisions.
The guidelines were brought to the attention of all other EANM Committees and of the European National Societies of Nuclear Medicine. The comments and suggestions from the Oncology, Radiopharmacy and Technologist Committees and the Israeli, Belgian and Spanish National Societies are highly appreciated and have been considered for these guidelines.
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This article does not describe any studies with human participants or animals performed by any of the authors.
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Egesta Lopci declares that she received a grant for immunotherapy research, unrelated to these guidelines, from AIRC (Associazione Italiana per la Ricerca sul Cancro).
All other authors declare no conflicts of interest.
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The European Association of Nuclear Medicine (EANM) is a professional nonprofit medical association that facilitates communication worldwide among individuals pursuing clinical and research excellence in nuclear medicine. The EANM was founded in 1985.
These guidelines are intended to assist practitioners in providing appropriate nuclear medicine care for patients. They are not inflexible rules or requirements of practice and are not intended, nor should they be used, to establish a legal standard of care.
The ultimate judgment regarding the propriety of any specific procedure or course of action must be made by medical professionals taking into account the unique circumstances of each case. Thus, there is no implication that an approach differing from the guidelines, standing alone, is below the standard of care. To the contrary, a conscientious practitioner may responsibly adopt a course of action different from that set out in the guidelines when, in the reasonable judgment of the practitioner, such course of action is indicated by the condition of the patient, limitations of available resources or advances in knowledge or technology subsequent to publication of the guidelines.
The practice of medicine involves not only the science but also the art of dealing with the prevention, diagnosis, alleviation, and treatment of disease. The variety and complexity of human conditions make it impossible to always reach the most appropriate diagnosis or to predict with certainty a particular response to treatment. Therefore, it should be recognized that adherence to these guidelines will not ensure an accurate diagnosis or a successful outcome. All that should be expected is that the practitioner will follow a reasonable course of action based on current knowledge, available resources, and the needs of the patient to deliver effective and safe medical care. The sole purpose of these guidelines is to assist practitioners in achieving this objective.
Appendices
Appendix 1
Drug interactions with mIBG
Extensive lists of medications with the theoretical potential to affect mIBG imaging have been previously published [36, 133, 134]. Several drugs listed in these publications are no longer commercially available. Moreover, the inclusion of drugs in these lists was based on the assumption that all drugs within a category could have the same effect on mIBG uptake as the drugs actually tested [54]. Medications that only indirectly affect circulating levels of norepinephrine, with an unknown specific mechanism of action, should not automatically be considered as likely to affect mIBG imaging results. This table presents the main categories of medications that can potentially affect mIBG uptake, with recommendations and comments regarding withdrawal based on the available evidence.
Category | Subcategory | Most commonly tested medication(s) | Level of evidencea | Strength of mIBG-inhibitory effect | Recommendations/comments |
---|---|---|---|---|---|
Drugs acting on adrenoreceptors | Beta blockers | Labetalol Propranolol | High | Labetalol: strong Others: none | Labetalol should be withheld Others: withholding not required |
Beta agonists | Salbutamol | Very low | None | Withdrawal not required | |
Alpha antagonists | Phenoxybenzamine | Low | Uncertain | Withdrawal probably not necessary | |
Alpha agonists | Clonidine | Very low | Uncertain | Withdrawal probably not necessary | |
Drugs affecting NE transport, retention or release | Tricyclic antidepressants | Desipramine | Medium | Moderate to strong | Should be withheld (otherwise, an alternative tracer for scanning should be considered) |
SSRIs and SNRIs | Fluvoxamine | Low | Moderate to strong for some agents | Consider withholding agents with documented effect on NET | |
Other anti-depressants | Trazodone | Very low | None | Insufficient evidence for recommendation | |
NE depleters | Reserpine | High | Strong | If still in clinical use, should be withheld | |
Sympathomimetics | Phenylpropanolamine | Low | Strong | Should be withheld (otherwise, an alternative tracer for scanning should be considered) | |
Monoamines | Cocaine | Moderate | Moderate | In case of suspected use, screen patients prior to mIBG scan | |
Calcium channel blockers | Nifedipine Cilnidipine | Medium | None | Effect (if any) is on release, not on mIBG uptake. Not necessary to withhold | |
Miscellaneous | Neuroleptics | Haloperidol | Very low | Uncertain | Uncertain |
Anaesthetics | Ketamine Xylazine Pentobarbital | Very low | Uncertain | Uncertain | |
Cardiac glycosides | Digoxin | Very low | Uncertain | Uncertain; withdrawal probably not necessary | |
Antiarrhythmics | Amiodarone | Medium | None | Effect (if any) beneficial. Not necessary to withhold |
Appendix 2
Thyroid blockade
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1.
123 I-mIBG
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(a)
Potassium iodate tablets (doses according to the patient’s age; protocol in use at Great Ormond Street Hospital for Children, London, UK):
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In a child between 1 month and 3 years of age: 42.5 mg (half a tablet) potassium iodate administered orally 1 h prior to mIBG injection, in the evening of that day, and on the following day after the mIBG scan (in total, three tablets in 2 days; in infants and young children the tablet can be crushed, dissolved in 2 mL of sterile water, and administered with a syringe to the back of the throat).
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In a child between 3 and 12 years of age: 85 mg (one tablet) potassium iodate administered orally 1 h prior to mIBG injection, in the evening of that day, and on the following day after the mIBG scan (in total, three tablets in 2 days).
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In patients above 12 years of age: 170 mg (two tablets) potassium iodate administered orally 1 h prior to mIBG injection, in the evening of that day, and on the following day after the mIBG scan (in total, three tablets in 2 days).
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(b)
Lugol’s iodine solution:
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Dose 0.6 mL of 5% solution per day.
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Given orally 2 days before 123I-mIBG injection, and continued for 3 days after injection.
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Should be diluted in any drink such as milk, or juice, as it may burn the throat if undiluted.
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The dose can be given as a single dose each day or split into 2 × 0.3 mL doses.
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-
(a)
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2.
131I-mIBG (in use at University Health Shreveport, Louisiana, USA):
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(a)
Protocol of administration: saturated solution of potassium iodide (SSKI) 30–60 min prior to injection of 131I-mIBG, orally from day 0, continued for a week.
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(b)
Dosage:
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Adult dosage: six drops of SSKI on day 0 and two drops of SSKI three times a day orally, beginning on the morning of day 1 and continuing for 1 week.
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Paediatric dosage:
<1 month: one drop orally 30–60 min prior to 131I-mIBG injection, then one drop orally in the morning of day 1, and daily for 1 week following injection.
1 month to 3 years: two drops orally 30–60 min prior to 131I-mIBG injection, then one drop orally twice a day beginning in the morning of day 1 and continuing for 1 week following injection.
3 to 18 years: three drops orally 30–60 min prior to 131I-mIBG injection, then one drop orally three times a day beginning in the morning of day 1 and continuing for 1 week following injection.
≥70 kg to adult: six drops orally 30–60 min after 131I-mIBG injection, then two drops orally three times a day beginning in the morning of day 1 and continuing for 1 week following injection.
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-
(a)
-
3.
Potassium perchlorate: in individuals sensitive to iodine, and if no other method for thyroid blockade is available.
Dose 10 mg/kg (maximum dose 500 mg, minimum dose 50 mg). Potassium perchlorate comes in 200 mg capsules and these should be opened and the contents either placed on a sugar lump (or similar) or dissolved in a flavoured drink. Potassium perchlorate is taken 1 h prior to 123I-mIBG injection and up to five times in the following 36 h.
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Bar-Sever, Z., Biassoni, L., Shulkin, B. et al. Guidelines on nuclear medicine imaging in neuroblastoma. Eur J Nucl Med Mol Imaging 45, 2009–2024 (2018). https://doi.org/10.1007/s00259-018-4070-8
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DOI: https://doi.org/10.1007/s00259-018-4070-8