Lutathera (lutetium Lu 177 dotatate)

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.

In 2018, the Food and Drug Administration (FDA) approved lutetium-177 (177Lu) DOTATATE (LUTATHERA, Advanced Accelerator Applications [Novartis]) for the treatment of somatostatin receptor positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs)...Less than 5 years later, in March 2022, 177Lu vipivotide tetraxetan (PLUVICTO, Advanced Accelerator Applications) received FDA approval for the treatment of prostatespecific membrane antigen-positive castration-resistant metastatic prostate cancer...As more radiotheranostic agents and applications get adopted in clinical practice, interventional radiologists are likely to get exposed to this field in a way or another. In this article, we discuss the fundamentals of radiotheranostic therapy and explore the expanding role interventional radiology (IR) is expected to play as an essential partner in modern oncology practice.

P1, N=27, Recruiting, Imperial College London | Trial completion date: Dec 2025 --> Feb 2029 | Trial primary completion date: Dec 2025 --> Jun 2026

Following PRRT, analysis of [68Ga]Ga-FAPI-04 PET/CT in well-differentiated NET is important to avoid misinterpretation. Benign fibrosis following treatment may show FAPI uptake as a possible source of false-positive findings on [68Ga]Ga-FAPI-04 PET/CT in the evaluation of NET.

Given the lack of significant effects on direct DNA repair or transcriptomic responses, our findings suggest that HSP90 inhibition radiosensitizes NET cells by inducing a pleiotropic effect on multiple stress-related pathways at the protein level, rather than solely through disruption of DNA damage response mechanisms. This effect is likely driven by loss of HSP90 function and subsequent cumulated unfolded protein and proteotoxic stress.

Baseline assessment reflects the patient's reserves and their post-PRRT state. Further, women are more prone to BM-related toxicity from PRRT. These insights can help optimize treatment strategies and improve patient outcomes in this population.

After undergoing surgical resection, intensity-modulated radiotherapy (IMRT), and systemic chemotherapy (cisplatin/etoposide), the patient experienced disease progression, prompting the initiation of targeted therapy with sunitinib...While initial tumor regression was observed, subsequent progression necessitated further stereotactic body radiotherapy (SBRT) and temozolomide. This case highlights the therapeutic potential of PRRT with Lu-177 DOTATATE in treating refractory SSTR-expressing ENB. A multidisciplinary approach that integrates surgery, radiotherapy, systemic therapy, and theragnostic strategies remains essential to optimizing patient outcomes.

P2, N=153, Not yet recruiting, RTOG Foundation, Inc. | Initiation date: Aug 2025 --> Nov 2025

Two RLT agents, [177Lu]Lu-DOTA-TATE (Lutathera®) and [177Lu]Lu-PSMA-617 (Pluvicto®), have received regulatory approval for the treatment of advanced gastroenteropancreatic neuroendocrine tumours and metastatic castration-resistant prostate cancer, respectively. Finally, we outline the main clinical challenges, including fixed dosing regimens, resistance, toxicity, and variability in patient selection and response assessment. Continued research to optimise radiopharmaceutical design, together with investment in infrastructure, workforce capacity, and international collaboration, will be essential to expand access and realise the full potential of RLT as a leading treatment strategy in modern oncology.

Short-course corticosteroid prophylaxis to prevent tumor flare reactions in high-risk patients with neuroendocrine tumors treated with 177Lu-DOTATATE did not appear to decrease the incidence of tumor flare reactions compared to previously reported numbers. Randomized, placebo-controlled trials looking at the use of corticosteroids to prevent tumor flare reactions in patients treated with 177Lu-DOTATATE are needed to fully elucidate the safety and efficacy of corticosteroids used in this setting and to determine the impact on treatment outcomes.

P1, N=60, Recruiting, Novartis Pharmaceuticals | Trial completion date: Feb 2026 --> Jul 2026 | Trial primary completion date: Dec 2025 --> Jun 2026

Given the rarity of pediatric bronchial carcinoid tumors, phase III clinical trials are unlikely, but this report supports the inclusion of LuTATE in multidisciplinary treatment planning. In conclusion, LuTATE therapy, guided by dosimetry calculations, offers a valid treatment option for pediatric bronchial carcinoid tumors, balancing efficacy, and safety in a challenging clinical scenario.