WIESBADEN-FRANKFURT — A clinical study in Wiesbaden-Frankfurt found that the investigational peptide receptor radionuclide therapy (PRRT) 225Ac-DOTA-LM3 is generally safe and shows antitumor activity in patients with advanced neuroendocrine tumors who have exhausted other treatments.
Twenty patients with well-differentiated neuroendocrine tumors grade 3 received 225Ac-DOTA-LM3 PRRT either as monotherapy—administered over nine cycles—or in TANDEM with the beta-emitting nuclide 177Lu across 32 cycles. Neuroendocrine tumors originate from neuroendocrine cells, most commonly in the gastrointestinal tract, pancreas, and lungs, and can metastasize. Patients with progressive forms of these tumors often face limited options after conventional therapies and approved beta-emitting PRRT have failed.
The treatment used a somatostatin receptor (SSTR) antagonist called DOTA-LM3 labeled with the alpha-emitting nuclide 225Ac. Alpha particles deliver high-energy radiation over a very short distance, which may help target tumor cells while limiting unnecessary exposure to nearby healthy tissues. After treatment, researchers monitored acute adverse events and long-term hematologic, renal, and hepatic toxicities, and evaluated molecular imaging response using post-PRRT SPECT/CT and follow-up 68Ga-DOTA-LM3 PET/CT scans.
Results showed the therapy was generally well-tolerated, with only mild, self-limiting acute adverse effects—mainly nausea—and a few cases of long-term toxicities including anemia, reduced white blood cell counts, and reduced platelet counts. Molecular imaging demonstrated complete remission in one patient, partial remission in 10, stable disease in two, and progressive disease in six; one patient died before post-PRRT imaging. At the time of analysis, 11 patients were alive with a median follow-up of seven months, and nine had died with a median survival of 18 months.
"In our study we explored the safety and efficacy of a novel PRRT approach that uses a somatostatin receptor (SSTR) antagonist (called DOTA-LM3) labeled to the alpha-emitting nuclide 225Ac to provide targeted therapy," nuclear medicine physician Elisabetta Perrone said. She added, "This cohort of patients was heterogeneous with respect to primary tumor site, prior treatments and number of alpha-PRRT cycles; nevertheless, alpha-PRRT with 225Ac-DOTA-LM3 (as monotherapy or in TANDEM), showed a manageable acute and long-term safety profile and encouraging antitumor activity, follow-up and survival outcomes."
Richard P. Baum, a nuclear medicine physician who guided the study, emphasized that "before it becomes more broadly available, larger 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." The therapy is currently offered only in highly specialized centers, including CURANOSTICUM Wiesbaden-Frankfurt and ICPO Center of Excellence for Advanced Radiomolecular Precision Oncology in Germany.