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

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

Perrone, Elisabetta et al.·Cancers·2025·Moderate EvidenceRetrospective Cohort
RPEP-13027Retrospective CohortModerate Evidence2025RETHINKTHC RESEARCH DATABASErethinkthc.com/research

Quick Facts

Study Type
Retrospective Cohort
Evidence
Moderate Evidence
Sample
N=35
Participants
Advanced NEN patients treated with Ac-225 DOTA-LM3 PRRT

What This Study 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.

Key Numbers

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 They Did This

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.

Why This Research 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 Bigger Picture

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

What This Study Doesn't Tell Us

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

Questions This Raises

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

Trust & Context

Key Stat:
35 patients, 57 cycles Largest published experience with Actinium-225 alpha-PRRT using somatostatin receptor antagonist for resistant neuroendocrine cancers
Evidence Grade:
Retrospective case series — the largest for this therapy. While not a controlled trial, it provides the most comprehensive safety and survival data available.
Study Age:
Published in 2025, covering treatment experience from 2018-2023 — the most comprehensive safety dataset for this therapy.
Original Title:
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.
Published In:
Cancers, 17(18) (2025)
Database ID:
RPEP-13027

Evidence Hierarchy

Meta-Analysis / Systematic Review
Randomized Controlled Trial
Cohort / Case-ControlFollows or compares groups over time
This study
Cross-Sectional / Observational
Case Report / Animal Study

Looks back at existing records to find patterns.

What do these levels mean? →

Frequently Asked 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 More on RethinkPeptides

Cite This Study

RPEP-13027·https://rethinkpeptides.com/research/RPEP-13027

APA

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

MLA

Perrone, Elisabetta, et al. "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, 2025. https://doi.org/10.3390/cancers17183070

RethinkPeptides

RethinkPeptides Research Database. "Peptide Receptor Radionuclide Therapy (PRRT) Using Actinium-..." RPEP-13027. Retrieved from https://rethinkpeptides.com/research/perrone-2025-peptide-receptor-radionuclide-therapy

Access the Original Study

Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.

This study breakdown was produced by the RethinkPeptides research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.