P=N/A, N=11, Completed, Central Hospital, Nancy, France | Not yet recruiting --> Completed

P=N/A, N=347, Completed, Novartis Pharmaceuticals | Trial completion date: Jan 2027 --> Jun 2024 | Trial primary completion date: Jan 2027 --> Jun 2024 | Active, not recruiting --> Completed

P1, N=10, Recruiting, University of Wisconsin, Madison | Trial completion date: Apr 2025 --> Feb 2026 | Trial primary completion date: Apr 2025 --> Feb 2026

P=N/A, N=25, Completed, Central Hospital, Nancy, France | Not yet recruiting --> Completed

On the basis of the findings, we recommend a starting dose of 200 mg BID for future studies, with the potential to escalate to 300 mg BID depending on patient tolerance. Further investigation in larger, randomized trials is warranted to assess the clinical efficacy of this combination and optimize dosing strategies.

P1, N=60, Recruiting, Novartis Pharmaceuticals | Trial completion date: Aug 2026 --> Apr 2028 | Trial primary completion date: Aug 2025 --> Mar 2027

P1, N=24, Recruiting, Peking University Cancer Hospital & Institute | Not yet recruiting --> Recruiting | Initiation date: Jan 2025 --> Sep 2024 | Trial primary completion date: Jul 2025 --> Dec 2025

P2, N=146, Recruiting, Institut du Cancer de Montpellier - Val d'Aurelle | Trial completion date: Sep 2029 --> Oct 2031 | Trial primary completion date: Mar 2025 --> Oct 2031

P1, N=18, Recruiting, Institut Claudius Regaud | Trial completion date: Jul 2025 --> Feb 2026 | Trial primary completion date: Jan 2025 --> Oct 2025

We discuss our strategy for the nutritional management of hypoglycaemia, reviewing the evidence for the use of cornstarch products and artificial nutrition. We discuss pharmacological management including diazoxide, somatostatin receptor antagonists (SSAs), everolimus and glucocorticoids, in addition to other therapeutic interventions such as peptide receptor radionuclide therapy (PRRT) and endoscopic ablation.

Radiotheranostics has transformed cancer care through its precision and adaptability, but challenges in radionuclide production, regulatory frameworks, and workforce training hinder broader adoption. Advances in isotopic pairing, next-generation radionuclides, and radiohybrid systems in preclinical and clinical settings hold promise to overcome these barriers. Collaborative efforts among academia, industry, and regulatory bodies are critical to accelerating innovation and optimizing clinical outcomes.

P1/2, N=56, Recruiting, National Cancer Institute (NCI) | N=42 --> 56

Despite symptomatic improvement, there was no significant survival benefit for those with pancreatic, liver, or nodal metastasis. A majority of patients who were treated with PRRT demonstrated clinical, radiological as well as biochemical positive responses warranting an earlier consideration for this well-tolerated treatment modality.

These findings provide evidence that SSTR2-based theranostics could have significant implications for the detection and treatment of HCC.

P3, N=240, Not yet recruiting, Novartis Pharmaceuticals

P=N/A, N=80, Not yet recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Initiation date: Dec 2024 --> Mar 2025

P1/2, N=39, Completed, Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori | Active, not recruiting --> Completed

P2, N=70, Terminated, Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori | Active, not recruiting --> Terminated; Enrollment target not reached

Based on the results of this trial, the addition of low-dose capecitabine to 177Lu-DOTATATE in advanced grade 1/2 GEP-NETs did not lead to superior radiographic responses. Further studies are needed to evaluate its potential role in high-grade NETs.

P2, N=41, Recruiting, Mayo Clinic | Trial completion date: Sep 2025 --> Jan 2031 | Trial primary completion date: Sep 2024 --> Jul 2026

We discuss our strategy for the nutritional management of hypoglycaemia, reviewing the evidence for the use of cornstarch products and artificial nutrition. We discuss pharmacological management including diazoxide, somatostatin receptor antagonists (SSAs), everolimus and glucocorticoids, in addition to other therapeutic interventions such as peptide receptor radionuclide therapy (PRRT) and endoscopic ablation.

Radionuclide therapy with lutetium-177 DOTATATE is employed for patients showing uptake in 68Ga-DOTA-SST PET/CT scans, while access to 131-MIBG therapy remains limited due to high costs and availability. Recent clinical trials have shown promise for systemic therapies such as sunitinib and cabozantinib, offering potential new options for patients with slow or moderate progression of PPGLs. These advancements underscore the potential of personalized and targeted therapies to improve outcomes in this challenging patient population.

The same concept could be applied to treatment of infection, by coupling the radioisotopes to ligands that target sterile or nonsterile inflammation. In our case, targeted peptide receptor radionuclide therapy showed remarkable resolution of inflammatory joint disease.

[177Lu]DOTATATE PRRT effectively reduces tumor functional activity in patients with SiNETs, with organ-specific responses highlighting the need for personalized treatment strategies to optimize efficacy and minimize toxicity.

P2, N=10, Not yet recruiting, OHSU Knight Cancer Institute | Trial completion date: Dec 2023 --> Dec 2025 | Trial primary completion date: Dec 2022 --> Dec 2025

In this work, [89Zr]Zr-DFO-TOC was synthesized with radiochemical yields ≥ 95% and was found to remain stable in vitro at extended time points. In vitro cell studies demonstrated a statistically significant difference between receptor binding and blocking experiments. The development of this work shows potential to positively impact patient care through the predictive dosimetry calculations for the FDA-approved therapeutic agent [177Lu]Lu-DOTA-TATE, while allowing for imaging at extended timepoints and should be studied further.

P1, N=24, Not yet recruiting, Peking University Cancer Hospital & Institute

Our exploratory analysis provides preliminary results showing that imaging indices of inter- and intra-tumor heterogeneity from pretreatment PET/CT images may potentially predict treatment efficacy in NET patients undergoing [177Lu]Lu-DOTA-TATE therapy. However, prospective evaluation in a larger cohort is needed to further assess whether a comprehensive characterization of tumor heterogeneity within a patient can help guide treatment decisions.

Peptide receptor radionuclide therapy (PRRT) using [177Lu-DOTA0,Tyr3]octreotate (177Lu-DOTATATE) represents an established treatment modality for somatostatin receptor-positive, locally advanced or metastatic gastroenteropancreatic neuroendocrine tumours (GEP NET) of grade 1 or 2...The results of these studies are likely to help address existing knowledge gaps in the coming years. This review describes the clinical practice, recent developments and future treatment options of PRRT in patients with grade 1 and 2 GEP NET.

The NETseq ensemble classifier identified PRRT-naïve GEP-NETs with high accuracy (≥92%) and demonstrated a potential role in early treatment response monitoring in the PRRT setting. This blood-based, non-invasive, multi-analyte molecular method could be developed as a valuable adjunct to conventional methods in the detection and treatment response assessment in NET patients.

Potential high-risk factors in order to treat effectively and prevent these toxicities in NET patients are presented including the management strategy. This review also discusses novel insights, perspectives, and recent advancements in predicting, preventing, and managing toxicity associated with PRRT, while offering prospective future research directions to minimize clinical toxicity and maximize the therapeutic benefits of PRRT as a treatment strategy for NET patients.

P1/2, N=65, Recruiting, Nationwide Children's Hospital | Trial primary completion date: Nov 2025 --> Nov 2027