68Ga-DOTATATE and 123I-mIBG as imaging biomarkers of disease localisation in metastatic neuroblastoma: implications for molecular radiotherapy.

Published on Nov 1, 2020in Nuclear Medicine Communications1.334
· DOI :10.1097/MNM.0000000000001265
Jennifer E. Gains9
Estimated H-index: 9
,
Matthew D. Aldridge5
Estimated H-index: 5
(UCLH: University College London Hospitals NHS Foundation Trust)
+ 4 AuthorsMark N. Gaze28
Estimated H-index: 28
Sources
Abstract
PURPOSE Iodine-131-labelled meta-iodobenzylguanidine (I-mIBG) and lutetium-177-labelled DOTATATE (Lu-DOTATATE) are used for molecular radiotherapy of metastatic neuroblastoma. These are taken up by the noradrenaline transporter (NAT) and the somatostatin receptor subtype 2 (SSTR-2), respectively. Scintigraphy of iodine-123-labelled meta-iodobenzylguanidine (I-mIBG) and gallium-68 DOTATATE (Ga-DOTATATE) PET are used to select patients for therapy. These demonstrate the extent and location of tumour, and avidity of uptake by cells expressing NAT and SSTR-2, respectively. This study compared the similarities and differences in the anatomical distribution of these two imaging biomarkers in an unselected series of patients with metastatic neuroblastoma undergoing assessment for molecular radiotherapy. METHODS Paired whole-body planar I-mIBG views and Ga-DOTATATE maximum intensity projection PET scans of metastatic neuroblastoma patients were visually compared. The disease extent was assessed by a semiquantitative scoring method. RESULTS Paired scans from 42 patients were reviewed. Ga-DOTATATE scans were positive in all patients, I-mIBG scans were negative in two. In two patients, there was a mismatch, with some lesions identified only on the I-mIBG scan, and others visible only on the Ga-DOTATATE scan. CONCLUSION Ga-DOTATATE and I-mIBG scans yield complementary information. For a more comprehensive assessment, consideration could be given to the use of both I-mIBG and Ga-DOTATATE imaging scans. Because of the heterogeneity of distribution of molecular targets revealed by these techniques, a combination of both I-mIBG and Lu-DOTATATE molecular radiotherapy may possibly be more effective than either alone.
📖 Papers frequently viewed together
80 Citations
2020
3 Authors (Ata Maaz, ..., Mehdi Djekidel)
70 Citations
References0
Newest
#1Elin Pauwels (Katholieke Universiteit Leuven)H-Index: 4
#2Matthias Van Aerde (Katholieke Universiteit Leuven)H-Index: 1
Last. Christophe Deroose (Katholieke Universiteit Leuven)H-Index: 30
view all 4 authors...
: The human norepinephrine transporter (hNET) is a transmembrane protein responsible for reuptake of norepinephrine in presynaptic sympathetic nerve terminals and adrenal chromaffin cells. Neural crest tumors, such as neuroblastoma, paraganglioma and pheochromocytoma often show high hNET expression. Molecular imaging of these tumors can be done using radiolabeled norepinephrine analogs that target hNET. Currently, the most commonly used radiopharmaceutical for hNET imaging is meta-[123I]iodobenz...
Source
#1Jennifer E. Gains (UCLH: University College London Hospitals NHS Foundation Trust)H-Index: 9
#2Veronica Moroz (University of Birmingham)H-Index: 9
Last. Mark N. Gaze (UCLH: University College London Hospitals NHS Foundation Trust)H-Index: 28
view all 9 authors...
PURPOSE: The objective of this phase IIa, open-label, single-centre, single-arm, two-stage clinical trial was to evaluate the safety and activity of 177-lutetium DOTATATE (LuDO) molecular radiotherapy in neuroblastoma. METHODS: Children with relapsed or refractory metastatic high-risk neuroblastoma were treated with up to four courses of LuDO. The administered activity was 75 to 100 MBq kg(-1) per course, spaced at 8- to 12-week intervals. Outcomes were assessed by the International Neuroblastom...
6 CitationsSource
#1Ruth Ladenstein (Boston Children's Hospital)H-Index: 53
#2Ulrike Pötschger (Community College of Rhode Island)H-Index: 43
Last. Holger N. Lode (Greifswald University Hospital)H-Index: 20
view all 24 authors...
To explore the effects of immunotherapy in the International Society of Paediatric Oncology Europe Neuroblastoma Group SIOPEN high-risk neuroblastoma 1 trial (HR-NBL1 trial), two cohorts were studied: one prior to and one after the introduction of dinutuximab beta. All patients received standard induction and high-dose therapy (HDT) with autologous stem cell rescue (ASCR); the local control comprised surgery and radiotherapy to the primary tumour site, followed by isotretinoin. A landmark timepo...
18 CitationsSource
#1Pezhman Shahrokhi (Tehran University of Medical Sciences)H-Index: 1
#2Alireza Emami-Ardekani (Tehran University of Medical Sciences)H-Index: 5
Last. Davood Beiki (Tehran University of Medical Sciences)H-Index: 16
view all 11 authors...
Objective(s): 68Ga-DOTATATE positron emission tomography (PET)/computed tomography (CT) has shown promising results in imaging of neural crest tumors (NCT). Herein, we compared the performance of 68Ga-DOTATATE PET/CT and 131I-MIBG single photon emission computed tomography (SPECT)/CT in the initial diagnosis, staging and follow-up of patients with NCTs. Methods: Twenty-five patients (males:females=8:17; age range=2–71 years) with clinically proven or suspicious neuroblastoma, pheochromocytoma (P...
1 CitationsSource
#1Jennifer E. Gains (UCLH: University College London Hospitals NHS Foundation Trust)H-Index: 9
#2Neil J. Sebire (Great Ormond Street Hospital for Children NHS Foundation Trust)H-Index: 98
Last. Mark N. Gaze (UCLH: University College London Hospitals NHS Foundation Trust)H-Index: 28
view all 5 authors...
Purpose Neuroblastoma may be treated with molecular radiotherapy, 131I meta-Iodobenzylguanidine and 177Lu Lutetium DOTATATE, directed at distinct molecular targets: Noradrenaline Transporter Molecule (NAT) and Somatostatin Receptor (SSTR2), respectively. This study used immunohistochemistry to evaluate target expression in archival neuroblastoma tissue, to determine whether it might facilitate clinical use of molecular radiotherapy.
7 CitationsSource
#1Marc Schulte (University of Duisburg-Essen)H-Index: 2
#2Johannes Köster (University of Duisburg-Essen)H-Index: 16
Last. Alexander Schramm (University of Duisburg-Essen)H-Index: 61
view all 4 authors...
The notion of cancer as a complex evolutionary system has been validated by in-depth molecular analyses of tumor progression over the last years. While a complex interplay of cell-autonomous programs and cell-cell interactions determines proliferation and differentiation during normal development, intrinsic and acquired plasticity of cancer cells allow for evasion of growth factor limitations, apoptotic signals, or attacks from the immune system. Treatment-induced molecular selection processes h...
6 CitationsSource
#1Zvi Bar-Sever (TAU: Tel Aviv University)H-Index: 13
#2Lorenzo Biassoni (Great Ormond Street Hospital for Children NHS Foundation Trust)H-Index: 7
Last. Francesco Giammarile (IAEA: International Atomic Energy Agency)H-Index: 23
view all 15 authors...
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...
27 CitationsSource
#1Mathieu Chicard (PSL Research University)H-Index: 6
#2Leo Colmet-Daage (PSL Research University)H-Index: 2
Last. Gudrun Schleiermacher (Curie Institute)H-Index: 46
view all 20 authors...
Purpose: Neuroblastoma displays important clinical and genetic heterogeneity, with emergence of new mutations at tumor progression. Experimental Design: To study clonal evolution during treatment and follow-up, an innovative method based on circulating cell-free DNA (cfDNA) analysis by whole-exome sequencing (WES) paired with target sequencing was realized in sequential liquid biopsy samples of 19 neuroblastoma patients. Results: WES of the primary tumor and cfDNA at diagnosis showed overlap of ...
47 CitationsSource
PurposeMore than two decades ago, an international working group established the International Neuroblastoma Response Criteria (INRC) to assess treatment response in children with neuroblastoma. However, this system requires modification to incorporate modern imaging techniques and new methods for quantifying bone marrow disease that were not previously widely available. The National Cancer Institute sponsored a clinical trials planning meeting in 2012 to update and refine response criteria for ...
85 CitationsSource
#1Ruth Ladenstein (Community College of Rhode Island)H-Index: 53
#2Ulrike Pötschger (Community College of Rhode Island)H-Index: 43
Last. Dominique Valteau-Couanet (University of Paris-Sud)H-Index: 24
view all 28 authors...
Summary Background High-dose chemotherapy with haemopoietic stem-cell rescue improves event-free survival in patients with high-risk neuroblastoma; however, which regimen has the greatest patient benefit has not been established. We aimed to assess event-free survival after high-dose chemotherapy with busulfan and melphalan compared with carboplatin, etoposide, and melphalan. Methods We did an international, randomised, multi-arm, open-label, phase 3 cooperative group clinical trial of patients ...
129 CitationsSource
Cited By3
Newest
#1Raghava KashyapH-Index: 12
#2Rakesh ReddyH-Index: 2
Last. Veni PrasannaH-Index: 1
view all 3 authors...
ABSTRACT In treatment of metastatic neuroblastoma, the central nervous system seems to act as a sanctuary leading to often unexpected relapse of disease. We present a case of neuroblastoma treated with chemotherapy and autologous stem cell transplantation only to relapse in central nervous system with meningeal metastases visualized on 68Ga-DOTATOC imaging.
Source
Neuroblastoma is the most common extracranial solid malignancy in children. At diagnosis, approximately 50% of patients present with metastatic disease. These patients are at high risk for refractory or recurrent disease, which conveys a very poor prognosis. During the past decades, nuclear medicine has been essential for the staging and response assessment of neuroblastoma. Currently, the standard nuclear imaging technique is meta-[123I]iodobenzylguanidine ([123I]mIBG) whole-body scintigraphy, ...
Source
#1Tara Haddad (U of T: University of Toronto)
#2Armaghan Fard-Esfahani (Tehran University of Medical Sciences)H-Index: 13
Last. Reza Vali (U of T: University of Toronto)H-Index: 12
view all 3 authors...
Neuroendocrine tumors (NETs) are rare in childhood. Neuroblastoma is the most common pediatric extracranial solid tumor, occurring >90% in children younger than 5 years of age. Pheochromocytoma and paraganglioma are rare NETs, causing hypertension in 0.5-2% of hypertensive children. Gastroenteropancreatic NETs can occur in children and are classified into carcinoids and pancreatic tumors. Nuclear medicine procedures have an essential role both in the diagnosis and treatment of NETs. Metaiodobenz...
Source
#2April-Louise Smith (UCLH: University College London Hospitals NHS Foundation Trust)H-Index: 1
Last. Mark N. GazeH-Index: 28
view all 9 authors...
Molecular radiotherapy, or targeted radionuclide therapy, uses systemically administered drugs bearing a suitable radioactive isotope, typically a beta emitter. These are delivered via metabolic or other physiological pathways to cancer cells in greater concentrations than to normal tissues. The absorbed radiation dose in tumour deposits causes chromosomal damage and cell death. A partner radiopharmaceutical, most commonly the same vector labelled with a different radioactive atom, with emission...
Source