Azedra (iobenguane I 131)

In HR-NBL, IGRT with reduced margins and a boost dose for residual lesions ≥ 1 cm3 demonstrated excellent locoregional control, comparable to modern literature.

Overall, 18% of germline SDHB mutation-carriers were diagnosed with PCC, all of which were unilateral. SDHB-associated PCC was associated with advanced and recalcitrant disease and was often MIBG positive. More studies are needed to better understand the clinical behavior of PCC in PGL-4.

18F-FDOPA PET/CT was found to be the superior functional imaging modality, with 100% lesion detection rate when compared to that of 68Ga-DOTATATE, 18F-FDG, 18F-FDA, and 123I-MIBG scans. While patients did not respond to chemotherapy or tyrosine kinase inhibitors, they responded to targeted radiotherapy using high-specific-activity 131I-MIBG (Azedra®) or 177Lu-DOTATATE (Lutathera®).

P1, N=45, Active, not recruiting, New Approaches to Neuroblastoma Therapy Consortium | Trial completion date: Jun 2024 --> Jun 2025

PPGLs patients with earlier onset age, SDHB or Cluster 1A-related gene mutations, negative 131I-MIBG imaging, or positive MGMT immunohistochemistry staining tend to have a higher Ki-67 index. Head and neck tumors, though smaller, exhibit a higher proliferation potential.

The combination of AURKA inhibition with 131I-MIBG treatment is active in resistant neuroblastoma models.

This comprehensive review delves into the current practice, discussing the use of the various Food and Drug Administration-approved SSTR-agonist positron emission tomography tracers and the predictive imaging biomarkers, and elaborating on 177Lu-DOTATATE peptide receptor radionuclide therapy including the evolving areas of posttherapy imaging practices and peptide receptor radionuclide therapy retreatment. SSTR-targeted imaging and therapy can also be used in patients with PPGL; however, this patient population has demonstrated the best outcomes from norepinephrine transporter-targeted therapy with 131I-metaiodobenzylguanidine. Metaiodobenzylguanidine theranostics for PPGL will be discussed, noting that in 2024 it became commercially unavailable in the United States. Therefore, the use and reported success of SSTR theranostics for PPGL will also be explored.

P1/2, N=0, Withdrawn, David Bushnell | N=50 --> 0 | Trial completion date: Oct 2025 --> Apr 2024 | Recruiting --> Withdrawn | Trial primary completion date: Oct 2025 --> Apr 2024

P1, N=44, Recruiting, University Hospital Southampton NHS Foundation Trust | Trial completion date: Nov 2023 --> Jul 2025 | Trial primary completion date: Nov 2023 --> Sep 2024

HSA-131I-MIBG is associated with a high DCR in patients with MPPGL, regardless of underlying genetic mutation.

P1, N=99, Active, not recruiting, Children's Oncology Group | Trial completion date: Sep 2023 --> Sep 2024

We demonstrate in a real-life clinical setting that all current therapies show reasonable efficacy in preventing disease progression, and this is equally true for patients with germline SDHB mutations.

Markers of lower NET and VMAT2 protein expression are associated with higher likelihood of response to I-MIBG therapy in patients with relapsed/refractory neuroblastoma. Increased VMAT2 protein expression is associated with a more differentiated disease phenotype.

P3, N=724, Active, not recruiting, Children's Oncology Group | Recruiting --> Active, not recruiting

P=N/A, N=47, Recruiting, Brigham and Women's Hospital | Not yet recruiting --> Recruiting

MIITOP showed acceptable tolerability in this heavily pretreated population and encouraging survival rates in VHR-NBL when followed by busulfan-melphalan.

In this paper, we review the literature data regarding 131-I-MIBG treatment for neuroblastoma, and report on doses and combinations used, tumor responses and toxicity. 131-I-MIBG is very effective against neuroblastoma, in particular if given to patients at diagnosis and in combination with chemotherapy, and it should be included in all induction regimens to improve early responses rates and consequently long-term survival.

P=N/A, N=47, Not yet recruiting, Brigham and Women's Hospital

P2, N=200, Recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: May 2023 --> May 2025 | Trial primary completion date: May 2023 --> May 2025

P1, N=99, Active, not recruiting, Children's Oncology Group | Phase classification: P=N/A --> P1

She was started on alpha blockade with doxazosin followed by beta blockade with metoprolol for medical management while hospitalized and discharged home with oncology and endocrinology follow-up...There is no curative treatment for metastatic pheochromocytoma and treatment with surgery, Iobenguane I-131, and chemotherapy are available to improve quality of life. Due to the increased risk of recurrence in patients with NF1, a multidisciplinary approach is essential during initial diagnosis and follow-up treatment. Increased post-operative monitoring may be warranted given the higher risk of recurrence in patients with NF1 who are diagnosed with initial pheochromocytoma.

P1, N=45, Active, not recruiting, New Approaches to Neuroblastoma Therapy Consortium | Recruiting --> Active, not recruiting

P2, N=60, Recruiting, Jubilant DraxImage Inc. | Trial primary completion date: Dec 2022 --> Dec 2023

P1, N=50, Recruiting, New Approaches to Neuroblastoma Therapy Consortium | Trial completion date: Mar 2023 --> Jun 2024 | Trial primary completion date: Sep 2022 --> Jun 2023

P=N/A, N=100, Suspended, Masonic Cancer Center, University of Minnesota | Trial completion date: Dec 2022 --> Dec 2025 | Recruiting --> Suspended | Trial primary completion date: Dec 2022 --> Dec 2025

Peripheral blood biomarkers relevant to radiation exposure demonstrate significant modulation after 131I-MIBG and concomitant radiation sensitizers impact extent of modulation. Biomarkers related to hematopoietic damage and apoptosis were associated with hematologic toxicity.

[211At]MABG has significant survival advantage in disseminated models of neuroblastoma. An alpha-particle emitting radiopharmaceutical may be effective against microscopic disseminated disease, warranting clinical development.

In mPPGL, HSA 131 I-MIBG is associated with high DCR regardless of underlying genetic mutation. Severe adverse events are infrequent but can be fatal.

P1, N=50, Recruiting, New Approaches to Neuroblastoma Therapy Consortium | N=32 --> 50

Key exclusion criteria include prior treatment with duration ≤3 wks (chemotherapy), ≤6wks (autologous stem cell transplant or therapeutic 131I-MIBG), ≤4wks (radiation therapy), or progressed while on anti-GD2; residual NB in the bone marrow only; and CNS/leptomeningeal disease in the prior 6 mo. Response rates will be assessed using the 2-sided binomial test at the 5% significance level; DoR, PFS, and OS will be estimated using Kaplan-Meier analysis. Adverse events will be graded per CTCAE.

When both radionuclide targets are expressed, the patients' comorbidity and treatment effectiveness should be valued together with the intensity uptake in the phenotypic image in order to choose the best therapeutic option. These preliminary retrospective results reinforce the need for a prospective, multicentric trial to be confirmed.

P2, N=200, Recruiting, Memorial Sloan Kettering Cancer Center | N=150 --> 200

All transplants utilized PBSC sources. All patients received 131I-MIBG (18 mCi/Kg) at day -21, besides a conditioning regimen consisting of Carboplatin (1500 mg/m2) and Vp16 (1200 mg/m2) for five consecutive days from day -7. Furthermore, Melphalan (210 mg/m2) was administered for three consecutive days from day -7... Different studies have suggested an efficient role of MIBG in NB patients as a pre-transplant conditioning regimen. These patients might rescue with high-dose conditioning regimens alongside the therapeutic MIBG. Finally, our study demonstrates the 18 mCi/Kg 131I-MIBG dose has a similar survival rate without more transplant-related complications, compared with the previous one using a lower 131I-MIBG dosage.

P2, N=150, Recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: May 2022 --> May 2023 | Trial primary completion date: May 2022 --> May 2023

P2, N=114, Completed, New Approaches to Neuroblastoma Therapy Consortium | Active, not recruiting --> Completed | Trial completion date: Jul 2021 --> Feb 2021 | Trial primary completion date: Jun 2021 --> Feb 2021

P2, N=60, Recruiting, Jubilant DraxImage Inc. | Trial primary completion date: Apr 2023 --> Dec 2022

Our studies showcase the use of biodosimetry gene expression panels as predictive biomarkers following early (72 h) and late (15 days) internal 131I exposure. Our findings also demonstrate the utility of our transcript panel to differentiate exposed from non-exposed individuals up to 15 days after exposure from internal 131I.

The risk of metastatic disease in cluster 2-related PPGL is 2.6%, being especially high in tumors with size ≥4cm and is associated with high mortality. One-third patients of NF1 with metastatic PPGL had presented in 2nd decade of life. Long-term studies are needed to formulate management recommendations.

16 patients received post-HDCT maintenance therapy with 13-CRA, IL-2, dinutuximab. Conclusion : Tandem HDCT/ASCT using busulfan-melphalan and thiotepa-cyclophosphamide combined with 131I-MIBG therapy was feasible and effective for high-risk neuroblastoma patients. But more efforts are needed to reducing TRM.

Combination of 177Lu-DOTATATE with chemotherapeutic agents might achieve worthwhile responses with low toxicity, encouraging survival in NB patients who have relapsed or are refractory to conventional therapy, including 131I-MIBG therapy. Imaging with 68Ga-DOTATATE PET/CT in such patients has a relatively high detection efficacy, demonstrating its potential use as an alternative imaging tool to conventional modalities such as 123I/131I-MIBG. However, further well-designed trials are highly warranted.

P2, N=60, Recruiting, Jubilant DraxImage Inc. | Trial completion date: Mar 2023 --> Apr 2025 | Trial primary completion date: Mar 2021 --> Apr 2023