Nuclear Medicine Review 2/2015-124I-MIBG: a new promising positron-emitting radiopharmaceutical for the evaluation of neuroblastoma

124I-MIBG: a new promising positron-emitting radiopharmaceutical for the evaluation of neuroblastoma

Angelina Cistaro1-3, Natale Quartuccio4, Federico Caobelli5, Arnoldo Piccardo6, Rosario Paratore7, Pietro Coppolino4, Alessandro Sperandeo7, Gaspare Arnone8, Umberto Ficola7

1Positron Emission Tomography Centre IRMET S.p.A., Euromedic Inc., Turin, Italy

2Coordinator of PET Pediatric AIMN InterGroup, Italy

3Associate researcher of Institute of Cognitive Sciences and Technologies, National Research Council, Rome, Italy

4Nuclear Medicine Unit, Department of Biomedical Sciences and of Morphologic and Functional Images, University of Messina, Italy

5Nuclear Medicine Unit, Hannover Medical School, Germany

6Nuclear Medicine Unit, Galliera Hospital, Genoa, Italy

7Department of Nuclear Medicine, La Maddalena Hospital, Palermo, Italy

8Nuclear Medicine Operating Unit, Civic Hospital, Palermo, Italy

The authors declare that they have no conflict of interest

[Received 1 I 2015; Accepted 31 III 2015]

Abstract

Neuroblastoma is the most common extra-cranial solid tumor in pediatric patients. Despite the established role of 123I-MIBG and 131I-MIBG scintigraphy in this tumor, only limited data are available regarding the use of 124I-metaiodobenzylguanidine (MIBG) positron emission tomography (PET)/computed tomography (CT). We present our preliminary experience with 124I-MIBG PET/CT: two pediatric patients affected by neuroblastoma, who underwent 124I-MIBG PET/CT for pre-therapy distribution evaluation and restaging purposes. We aimed to evaluate whether 124I-MIBG PET/CT can detect as many or more neuroblastoma lesions than 123I/131I-MIBG imaging. Our cases show promising results, although further validation and standardization of 124I-MIBG PET/CT are required.

KEY words: neuroblastoma, 124I-MIBG PET/CT, bone metastases, 123I-MIBG scan, radiometabolic therapy

Nuclear Med Rev 2015; 18, 2: 102-106

Background

Neuroblastoma (NB) is the most common extra-cranial solid tumor in pediatric patients and originates from sympathetic cells derived from the neural crest. Bone and bone marrow metastases are quite common and, if present, result in a poor prognosis [1,2]. Many studies have been reported the important role of 123I-Meta-iodobenzylguanidine (MIBG) at the time of first staging and at the evaluation of treatment response, especially after induction chemotherapy [3-5]. Moreover, 123I-MIBG scan Is required when NB relapse is suspected and may establish the basis for the use of a targeted radionuclide therapy with 131I-MIBG [6]. The principal limitation of conventional nuclear medicine in neuroblastoma (mainly 123I-MIBG scan) is related to its relative low spatial resolution when compared with other radiological and functional techniques such as CT, MRI and PET, similarly to what happens in other pediatric tumors [7-13].

MIBG labeled with 124I, a positron emitting isotope suitable for PET imaging, got increased interest in clinical practice [14-17]. The target of this radiocompound should be the capability of binding noradrenalin receptors as it happens with 123I-MIBG, but with a higher image quality and sensitivity granted by PET hardware [14]. However, limited data exist about the diagnostic accuracy of 124I-MIBG PET in NB.

We present the preliminary experience of the PET Pediatric AIMN (Italian Association of Nuclear Medicine) InterGroup with 124I-MIBG PET/CT in two pediatric patients diagnosed with neuroblastoma in order to highlight the improvement in diagnostic accuracy provided by 124I-MIBG PET/CT compared to the conventional imaging work-up assessing whether 124I-MIBG PET/CT could detect as many or more neuroblastoma lesions than 123I/131I-MIBG imaging.

Case series

Case 1. Taking advantage of the better spatial resolution of 124I-MIBG PET/CT

Patient No. 1 (10-year-old female) came to our observation with diagnosis of poorly differentiated abdominal neuroblastoma – stage III –with involvement of the left kidney and the homolateral adrenal gland. The patient had undergone neoadjuvant chemotherapy (clsplatln, etoposlde and VP 16) before radical resection of the large abdominal mass. One year after surgery, the patient was referred for 131I-MIBG therapy (dose: 10 GBq) for a pulmonary relapse detected by a computed tomography (CT) exam. The 123I-MIBG pre-therapy and the 131I-post-therapy whole body scans depicted a single focal round-shaped uptake In the right lung. Aweek later, the child was proposed to scan with the experimental radiopharmaceutical 124I-MIBG for compassionate use, regulated by Legislative Decree No. 219/2006. After receiving written consent from the parents, the patient was evaluated by PET/CT at 24h and 48h after the administration of 50 MBq of 124I-MIBG (radiochemical purity > 95%) (Fig. 1). The PET/CT study (Fig. 2) confirmed the finding detected by both 123I-MIBG scintigraphy and 131I-post-therapy whole body scan allowing a better characterization and localization of the finding in the basis of the right lung.

Figure 1A-F. 123I-MIBG planar images (A, B): posterior images, after 4 h (A) and 24 h (B) from radiopharmaceutical intravenous administration, documenting a lesion in the posterior region of the right pulmonary basis. 131I-MIBG post-therapy scan (C, D): anterior images, acquired 24 h (C) and 48 h (D) after injection. Uptake in the right lung is consistent with pulmonary recurrence. 124I-MIBG Maximum Intensity Projection (MIP) images after 24h (E) and 48h (F) show the same finding

Figure 2A-C. Axial 123I-MIBG 24 h-SPECT image (A) and PET/CT fusion images taken at 24h (B) and 48h (C) documented the pulmonary lesion in the right lower pulmonary lobe. Of note the increased uptake over the time in the 124I-MIBG PET/CT images

Afterwards, the patient underwent metastasectomy and the disease had afavorable course confirmed by a subsequent 123I-MIBG scintigraphy and a chest CT performed three and six months later, respectively. Nevertheless, the patient developed lumbar pain and signs of paraparesis a few months later, and a whole body CT with contrast medium revealed diffuse metastases to both lungs, abdominal lymph nodes and the fifth lumbar vertebra. Therefore the patient was referred for a second course of 131I-MIBG therapy. The 131I-MIBG post-therapy whole body scan (Fig. 3) was able to highlight all the lesions demonstrated by the CT scan, but pre-therapy 124I-MIBG PET/CT yielded a very good definition of the extent of disease (Fig. 4), demonstrating also the involvement of the medullary canal by the lesion located in the L3 vertebra, explaining the origin of the symptomatology of the patient, and revealed faint foci in L1, L4, L5 and sacrum (Fig. 5). On the basis of the clinical condition and imaging findings, the patient underwent a further treatment with 131 I-MIBG, with a delivered dose of 10 GBq (270 mCi).

Figure 3A-C. Multiple pulmonary lesions evidenced by the 124I-MIBG PET/CT Maximum Intensity Projection (MIP) image (A) and the posterior views of 131I-MIBG post-therapy scan acquired 24 h (B) and 48 h (C) after injection

Figure 4A. Sagittal CT, 124I-MIBG PET and fused PET/CT images; B. Axial co-registered CT image at the level of the third lumbar vertebra; C. Axial 124I-MIBG PET/CT view of L3.124I-MIBG PET/CT shows the same metastatic involvement of L3, as shown in figure 3 but with a dramatically improved definition, demonstrating the intracanal and the extra canal components of the lesion

Figure 5A-D. Multiple metastatic lesions in patient No. 1 highlighted by 124I-MIBG PET/CT: L1 (A), L4 (B), L5 (C) and sacrum (D)

Case 2. Depiction of all metastatic sites in one single full-body exam

Patient No. 2 was a 6-year-old boy with left adrenal gland neuroblastoma (stage IV) diagnosed when he was 1-year-old. The pathologic history had showed persistent bone disease involvement although the patient had already been treated with surgery, radiotherapy chemotherapy and auto-transplantation over the years. After performing a follow-up 123I-MIBG scintigraphy in another center for restaging purposes, he was referred to our department to receive a course of 9.9 GBq (270 mCi) 131I-MIBG. The 131I-MIBG post-therapy scan showed diffuse osseous disease (Fig. 6A, B) Including the skull, the left scapula, several vertebrae, the right and left iliac bones, the ischiatic spine, the proximal part of the left tibia and the bone marrow canal of the right femur. After gaining informed consent from the patient, 124I-MIBG PET/CT was also performed for compassionate use and was able to visualize the same lesions as detected by the planar scintigraphy with 131I-MIBG (Fig. 6C-F) clearly providing images with better spatial resolution in all the bone districts.

Figure 6A-F. 131I-MIBG post-therapy total body scan, anterior (A) and posterior (B) images: scintigraphic pattern consistent with multiple bone metastases (some of the lesions are evidenced by arrows: skull, pelvis and femur). 124I-MIBG PET/CT was also performed and was able to visualize the same number of metastases. Axial 124I-MIBG PET/CT fusion images showing some of the metastatic lesions with a dramatically improved definition; C. Skull; D-E. Pelvis; F. Right femur (an involvement of the left femur is also evident)

Discussion

Although MIBG, radiolabeled with 123I, has high sensitivity (around 90%) and specificity close to 100% in the diagnosis of neuroblastoma [17], nevertheless an important role of labeled MIBG is also prospectively to evaluate the feasibility of 131I-MIBG radiometabolic therapy, which can be an additional therapeutic option in case of disseminated metastatic disease in which tumor cells have retained the capability of concentrating MIBG [6].

From this point of view, 124I-MIBG PET/CT represents a potential method to estimate radiation dose to normal organs, as well as tumors, prior to 131I-MIBG treatment and provide a more accurate quantification of tracer distribution because of its favorable characteristics, such as full-body tomographic capability from PET and a similar half-life (4.2 days) to 131I (8.02 days) [15].

Despite this important aspect, only few reports published in literature regarded the use of 124I-MIBG in adult patients with neural crest tumors [14, 16] and, to the best of our knowledge, only one child with neuroblastoma has been studied with 124I-MIBG PET/CT so far [18], providing data on dosimetry. Organ-absorbed doses for the salivary glands, heart wall and liver were 98.0 Gy, 36.5 Gy, and 34.3 Gy respectively whereas tumor-absorbed dose range was 143.9-1,641.3 Gy [18].

Many other studies investigated the role of PET/CT using other tracers such as 18F-DOPA [7, 19], 68Ga-labelled somatostatin analogues and 18F-FDG in patients with neuroblastoma [20]. Anyway, although these tracers can provide an excellent diagnostic accuracy in patients affected by neuroblastoma, nevertheless the labeled pharmaceutical has a metabolic behavior which is similar but not equal to Iodine-labeled MIBG.

In our series, we investigated if 124I-MIBG PET/CT could be considered a valuable tool in the diagnostic work-up of pediatric patient with advanced neuroblastoma.

From our experience, 124I-MIBG PET/CT provides high-resolution images and may offer valuable information regarding the extension of the lesion and the involvement of different types of tissue, addressing the most appropriate clinical management between surgical treatment and medical therapy [21]. In the present study with the limit of lack of SPECT/CT, we could compare in our patients images obtained with 123I-MIBG scintigraphy, 131I-MIBG scintigraphy and with 124I-MIBG PET/CT, with the latter providing the same e information about the tumor location In the case of the single round-shaped pulmonary lesion (patient n. 1).

In patient No. 1, the first 124I-MIBG PET/CT not only confirmed the finding detected by both 123I-MIBG scintigraphy and 131I-MIBG post-therapy scan, but allowed a better characterization and localization of the finding in the basis of the right lung, helping the clinical staff in the decision of performing a metastasectomy. Furthermore, the second 124I-MIBG PET/CT, performed in case No. 1, provided a very accurate definition of the extent of disease demonstrating the intracanal and the extra canal components of the lesion located at the level of L3 and detected a higher number of lesion (L1, L4, L5 and sacrum) In comparison to 131I-MIBG and CT. The findings of 124I-MIBG PET/CT were useful for the clinicians to link the symptomatology of the patient (lumbar pain and signs of paraparesis) to the pathologic involvement of the medullar canal.

Since metastatic spread of neuroblastoma may occur over the full length of the skeleton and since MIBG does not present uptake in the brain, 124I-MIBG gives excellent images of the skull and so is useful to detect secondary lesions in this anatomical region, which is a relatively freguent site of metastasis. Likewise, 124I-MIBG PET/CT should be performed in full body modality from the vertex of the skull to the feet.

A possible limitation in evaluating pediatric patients with 124I-MIBG PET/CT is the relatively higher radiation dose delivered (0.25 mSv/MBg) when compared to 123I-MIBG (0.019 mSv/MBg). Nevertheless, the improved characteristics of modern PET/CT scanners allow limiting the administered dose while maintaining an adeguate image quality [22]. Moreover, the additional dose can be considered negligible by comparison if 124I-MIBG is performed as a pre-therapy evaluation tool before 131I-MIBG treatment.

Although there is lack of information in literature, this preliminary experience shows promising results for 124I-MIBG PET/CT; anyway, a large validation and a standardization of the technigue is needed, such as for the optimal timing of 124I-MIBG PET imaging acguisition.

Multicenter investigations would be desirable, in order to foster the possible role of this technigue in evaluating patients with neuroblastoma. At present, we could at least suggest to perform a 124I-MIBG PET/CT as a pre-therapy examination, given the high diagnostic accuracy demonstrated by our cases, and for restaging, especially when doubtful findings are evidenced by scintigraphic imaging with 123I- or 131I-MIBG.

References

  1. Matthay KK, Shulkin B, Ladenstein R et al. Criteria for evaluation of disease extent by 123l-metaiodobenzylguanidine scans in neuroblastoma: a report for the International Neuroblastoma Risk Group (INRG) Task Force. Br J Cancer 2010; 102: 1319-1326.
  2. Piccardo A, Lopci E, Conte M et al. PET/CT imaging in neuroblastoma. Q J Nucl Med Mol Imaging 2013; 57: 29-39.
  3. Jacobson AF, Deng H, Lombard J, Lessig HJ, Black RR. 1231-Meta-iodobenzylguanidine scintigraphy for the detection of neuroblastoma and pheochromocytoma: results of a meta-analysis. J Clin Endocrinol Metab 2010; 95: 2596-606.
  4. Matthay KK, Edeline V, Lumbroso J 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: 2486-2491.
  5. Sharp SE, Shulkin BL, Gelfand MJ, Salisbury S, Furman WL. 123I-MIBG scintigraphy and 18F-FDG PET in neuroblastoma. J Nucl Med 2009; 50: 1237-1243.
  6. Taggart D, Dubois S, Matthay KK. Radiolabeled metaiodobenzylguanidine for imaging and therapy of neuroblastoma. Q J Nucl Med Mol Imaging 2008; 52: 403-418.
  7. Lopci E, Piccardo A, NanniCetal. 18F-DOPA PET/CT in neuroblastoma: comparison of conventional imaging with CT/MR. Clin Nucl Med 2012; 37: e73-e78.
  8. Piccardo A, Lopci E, Conte M 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.
  9. Bombardieri E, Coliva A, Maccauro M et al. Imaging of neuroendocrine tumours with gamma-emitting radiopharmaceuticals. Q J Nucl Med Mol Imaging 2010; 54: 3-15.
  10. Skanjeti A, Guerra L, Cistaro A. 18F-FDG-PET/CT in pediatric lymphoma. In: Cistaro A (ed.). Atlas of PET/CT in pediatric patients. Springer, Milan 2014: 39-59.
  11. Quartuccio N, Cistaro A. Primary bone tumors. In: Cistaro A (ed.). Atlas of PET/CT in pediatric patients. Springer, Milan 2014: 67-86.
  12. Cistaro A, Fania R Valentini MC. 18F-FDG in the imaging of bran tumors In: Cistaro A (ed.). Atlas of PET/CT in pediatric patients. Springer, Milan 2014: 165-179.
  13. Papathanasiou ND, Gaze MN, Sullivan K et al. 18F-FDG PET/CT and 123I-metaiodobenzylguanidine imaging in high-risk neuroblastoma: diagnostic comparison and survival analysis. J Nucl Med 2011; 52: 519-525.
  14. Ott RJ, Tait D, Flower MA, Babich JW, Lambrecht RM. Treatment planning for 131I-mIBG radiotherapy of neural crest tumours using 124I-mIBG positron emission tomography. Br J Radiol 1992; 65: 787-791.
  15. Lee CL, Wahnishe H, Sayre GA et al. Radiation dose estimation using preclinical imaging with 124I-metaiodobenzylguanidine (MIBG) PET. Med Phys 2010; 37: 4861-4867.
  16. Hartung-Knemeyer V, Rosenbaum-Krumme S, Buchbender C et al. Malignant pheochromocytoma imaging with [124I]mIBG PET/MR. J Clin Endocrinol Metab 2012; 97: 3833-3834.
  17. 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.
  18. Huang SY, Bolch WE, Lee C 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. 2014; 17: 284-294. doi: 10.1007/s11307-014-0783-7.
  19. Lu MY, Liu YL, Chang HH et al.; National Taiwan University Neuroblastoma Study Group. Characterization of neuroblastic tumors using 18F-FDOPA PET. J Nucl Med 2013; 54: 42-49.
  20. Mueller WR Coppenrath E, Pfluger T. Nuclear medicine and multimodality imaging of pediatric neuroblastoma. Pediatr Radiol 2013; 43: 418-427.
  21. Seo Y, Gustafson WC, Dannoon SF et al. Tumor dosimetry using [124I]m-iodobenzylguanidine microPET/CT for [131I]m-iodobenzylguanidine treatment of neuroblastoma in a murine xenograft model. Mol Imaging Biol 2012; 14: 735-742.
  22. Boellaard R, O’Doherty MJ, Weber WA et al. FDG PET and PET/CT: EANM procedure guidelines for tumour PET imaging: version 1.0 Eur J Nucl Med Mol Imaging 2010; 37: 181-200.

Correspondence to:
Angelina Cistaro, MD,
Positron Emission Tomography Centre IRMET S.p.A.
Euromedic Inc.
V. O. Vigliani 89/A, 10138 Turin, Italy
Tel +39 01 13 160 159
Fax+39 01 13 160 828
E-mail: a.cistaro@irmet.com

Regulations

Important: This website uses cookies. More >>

The cookies allow us to identify your computer and find out details about your last visit. They remembering whether you've visited the site before, so that you remain logged in - or to help us work out how many new website visitors we get each month. Most internet browsers accept cookies automatically, but you can change the settings of your browser to erase cookies or prevent automatic acceptance if you prefer.

By "Via Medica sp. z o.o." sp.k., Świętokrzyska 73 street, 80–180 Gdańsk, Poland

tel.:+48 58 320 94 94, faks:+48 58 320 94 60, e-mail: viamedica@viamedica.pl