A new type of peptide receptor radionuclide therapy (PRRT) appears to be safe for patients with metastatic neuroendocrine tumors who have exhausted conventional treatment options. This new approach, presented at the 2026 Society of Nuclear Medicine Annual Meeting, resulted in partial remission of disease in the majority of patients with advanced neuroendocrine tumors.
Neuroendocrine tumors are a type of cancer that starts in neuroendocrine cells (most commonly found in the gastrointestinal tract, pancreas, and lungs) and can spread to other parts of the body. Patients with aggressive neuroendocrine tumors often have limited treatment options, especially after failure of conventional treatments or approved beta-emitting PRRT. Their prognosis is generally poor and there is a clear unmet need for new treatment strategies.
These patients can be very difficult to treat because they are already undergoing different types of treatments. Our study investigated the safety and efficacy of a novel PRRT approach that uses a somatostatin receptor (SSTR) antagonist (termed DOTA-LM3) labeled with the alpha-emitting nuclide 225Ac to deliver targeted therapy. Because alpha particles deliver high-energy radiation over very short distances, this aspect may help target tumor cells while limiting unnecessary exposure to nearby healthy tissue, and the balance between efficacy and toxicity is therefore an important consideration for patients undergoing systemic therapy. ”
Elisabetta Perrone, MD, Nuclear Medicine Physician, Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
Twenty patients with different primary sites of grade 3 well-differentiated neuroendocrine tumors received 225Ac-DOTA-LM3 PRRT as monotherapy (9 cycles) or in tandem therapy with the beta-emitting nuclide 177Lu (32 cycles). After receiving treatment, acute adverse events and long-term hematologic, renal, and hepatic toxicities were monitored and graded. Molecular imaging responses were evaluated with post-PRRT SPECT/CT and follow-up 68Ga-DOTA-LM3 PET/CT, and survival rates were calculated.
The treatment was generally well tolerated, both as monotherapy and as tandem therapy, with only mild, self-limited acute side effects, primarily nausea, and only a few long-term toxicities, including anemia, decreased white blood cell count, and decreased platelet count. Molecular imaging showed one patient with complete remission, 10 with partial remission, two with stable disease, and six with progressive disease. One patient experienced clinically fatal progression before post-PRRT imaging. At the time of analysis, 11 patients were alive (median follow-up, 7 months) and 9 had died (median survival, 18 months).
“Although this patient cohort was heterogeneous with respect to primary tumor site, prior treatment, and number of alpha-PRRT cycles, alpha-PRRT combined with 225Ac-DOTA-LM3 (monotherapy or TANDEM) demonstrated a manageable acute and long-term safety profile and promoted antitumor activity, follow-up, and survival outcomes,” Perrone said. “Based on this real-world experience, α-PRRT may offer a potential additional option for selected patients whose tumors still express somatostatin receptors, as documented with pre-treatment 68Ga-DOTA-LM3 PET/CT.”
225Ac-DOTA-LM3 PRRT is considered an investigational drug and is currently offered only at highly specialized centers (including the ICPO Advanced Radiation and Molecular Precision Oncology Center of Excellence Curanosticum Wiesbaden Frankfurt in Germany), where research is being conducted under the direction of nuclear medicine physician Richard P. Boehm, MD, and is typically performed within a controlled clinical, compassionate use, or individual treatment setting.
“Large multicenter studies and prospective clinical trials are needed to confirm efficacy, better define safety, optimize dosing, and identify which patients are most likely to benefit before it becomes more widely available,” Bohm said.
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Society of Nuclear Medicine and Molecular Imaging
