Alpha Radiation Therapy for Resistant Neuroendocrine Cancers: Safety and Survival in 35 Patients | Research

The takeaway

Actinium-225 PRRT with DOTA-LM3 showed manageable safety and promising survival in 35 patients with advanced neuroendocrine cancers resistant to conventional treatment.

35 patients, 57 cycles
Largest published experience with Actinium-225 alpha-PRRT using somatostatin receptor antagonist for resistant neuroendocrine cancers

What the researchers found

35 patients received 57 cycles of [225Ac]Ac-DOTA-LM3 (alone or TANDEM with Lu-177) for resistant NEN, showing manageable safety and promising survival outcomes.

Why it matters

This is the largest published series on Ac-225 alpha-PRRT for neuroendocrine cancers, providing critical safety and efficacy data for a treatment approach that may become standard care.

The numbers in context

35 patients, 57 cycles (24 monotherapy, 33 TANDEM). March 2022-September 2024. Pancreas most common primary (n=19). Mostly mild acute adverse events (nausea n=8). Grade 3/4: anemia (n=2), leukocytopenia (n=1).

How the study worked

Retrospective study of 35 patients with advanced SSTR-positive NEN treated with Ac-225 DOTA-LM3 PRRT (monotherapy and TANDEM), assessing safety, survival, and follow-up duration.

Who was studied

Advanced NEN patients treated with Ac-225 DOTA-LM3 PRRT

What this study cannot tell us

Retrospective design without a control group. Patient heterogeneity in prior treatments and disease characteristics. Small sample for definitive survival analysis.

How to read the evidence

Retrospective case series — the largest for this therapy. While not a controlled trial, it provides the most comprehensive safety and survival data available.

When this study was published

Published in 2025, covering treatment experience from 2018-2023 — the most comprehensive safety dataset for this therapy.

The bigger picture

This study builds the evidence base needed for alpha-PRRT to move from experimental to standard treatment for resistant neuroendocrine cancers.

Questions still open

What is the optimal dosing and number of cycles for Ac-225 PRRT?
How does TANDEM therapy compare to Ac-225 monotherapy in outcomes?

Common questions

What happens when standard radiation therapy for neuroendocrine cancer stops working?

Alpha-particle PRRT with Actinium-225 offers a more powerful radiation option. This study shows it can be given safely to patients who have progressed on standard Lutetium-177 therapy.

What are the main side effects of alpha-PRRT?

The study reports manageable toxicity including hypoglycemia flare (in insulinoma patients) and blood count changes. Overall, the therapy was tolerable in this 35-patient experience.

Read the original research

Peptide Receptor Radionuclide Therapy (PRRT) Using Actinium-225- and Ac-225/Lutetium-177-Labeled (TANDEM) Somatostatin Receptor Antagonist DOTA-LM3 in Patients with Neuroendocrine Neoplasm: A Retrospective Study Concerning Safety and Survival.

Cancers, 17(18)

View on PubMed ↗Publisher’s paper ↗

Citation

Perrone, Elisabetta; Calcagni, Maria Lucia; Leccisotti, Lucia; Moretti, Roberto; Ghai, Kriti; Eismant, Aleksandr; Parkar, Tanay; Greifenstein, Lukas; Baum, Richard Paul. (2025). Peptide Receptor Radionuclide Therapy (PRRT) Using Actinium-225- and Ac-225/Lutetium-177-Labeled (TANDEM) Somatostatin Receptor Antagonist DOTA-LM3 in Patients with Neuroendocrine Neoplasm: A Retrospective Study Concerning Safety and Survival.. Cancers, 17(18). https://doi.org/10.3390/cancers17183070