Azedra (iobenguane I 131)

P2, N=118, Not yet recruiting, New Approaches to Neuroblastoma Therapy Consortium

Radiopharmaceuticals such as 131I-MIBG and 177Lu-DOTATATE continue to play a pivotal role, achieving disease control in many patients. Cytotoxic regimens, particularly temozolomide, remain relevant, with some studies suggesting that SDHB-mutated PPGLs demonstrate a heightened sensitivity associated with MGMT promoter hypermethylation and reduced MGMT expression. Targeted agents are increasingly important: multi-kinase inhibitors such as sunitinib, anlotinib, and cabozantinib have shown meaningful activity. The landmark approval of belzutifan, a HIF-2α inhibitor, in 2025 represents the first oral targeted therapy for advanced/metastatic PPGL, which is particularly relevant for pseudohypoxic Cluster 1 tumors...This review summarizes current evidence and highlights ongoing clinical trials, underscoring a paradigm shift toward precision medicine and rational combination strategies. Collectively, these advances bring cautious optimism that metastatic PPGLs may soon become a more manageable chronic disease with improved survival and quality of life.

This study aims to investigate the therapeutic potential of 131I-MIBG and the PARP inhibitor fluzoparib monotherapies and their combination on two distinct PC12-derived stable cell lines: PC12-NET cells and PC12-NET-SDHB cells...The specificity of PC12-NET cells to the 131I-MIBG was confirmed through desipramine inhibition assays...The combined of 131I-MIBG with PARP inhibitor demonstrated a synergistic antitumor effect in PC12-NET cells. While PC12-NET-SDHB cells display comparable sensitivity to 131I-MIBG as PC12-NET cells, they exhibited heightened responsiveness to PARP inhibitor treatment.

P=N/A, N=15, Completed, Masonic Cancer Center, University of Minnesota | Suspended --> Completed | N=100 --> 15

This study highlights the critical influence of the compounds' chemical structure on NET and OCT affinities. Structural modifications that reduce OCT-mediated uptake while maintaining high NET affinity could improve the specificity and theranostic potential of NET-targeting ligands. These findings provide insights for designing next-generation radiotracers with enhanced selectivity and clinical utility.

P1, N=44, Active, not recruiting, University Hospital Southampton NHS Foundation Trust | Trial completion date: Jul 2025 --> Nov 2025

P3, N=750, Recruiting, Children's Oncology Group | Trial completion date: Sep 2026 --> Sep 2030 | Trial primary completion date: Sep 2026 --> Sep 2030

P3, N=750, Recruiting, Children's Oncology Group | Active, not recruiting --> Recruiting

In this head-to-head comparison, [18F]MFBG PET/CT demonstrates excellent diagnostic performance in neuroblastoma, comparable to SSTR-targeted PET. These findings suggest that routine dual-tracer imaging is not recommended and should be reserved for patients based on specific therapeutic consideration, including the clinical need for [131I]MIBG radionuclide therapy or peptide receptor radionuclide therapy (PRRT).

At the age of 49, he received 131I-MIBG therapy for the recurrence of pheochromocytoma with bone metastasis. In conclusion, while 177Lu-DOTATATE therapy is generally considered safe, our findings underscore the potential risks of fatal crisis after therapy. Careful monitoring of patients with PPGL should be performed after treatment.

HMGB1 was released from neuroblastoma cells but not from normal cells after 131I-MIBG administration. A combination of 131I-MIBG and immunotherapy may be feasible.

Even at doses 20 times lower than [131I]MIBG, [211At]MABG demonstrated superior antitumor efficacy without inducing substantial weight loss. These findings suggest that [211At]MABG may serve as a promising alternative for treating malignant PCC.