Dramatic Tumor Response to Dual-Radionuclide Peptide Therapy in a Patient with Treatment-Resistant Pancreatic Neuroendocrine Cancer

A 58-year-old woman with rapidly progressive, therapy-refractory neuroendocrine pancreatic tumor (grade G3) with extensive liver, bone, and lymph node metastases received three cycles of TANDEM peptide receptor radionuclide therapy (PRRT) using concurrently administered [177Lu]Lu-DOTA-LM3 and [225Ac]Ac-DOTA-LM3, a somatostatin receptor antagonist. The treatment produced complete regression of bone and lymph node metastases, significant reduction in liver metastases and hepatomegaly, and improvement in the primary pancreatic tumor. Partial remission was confirmed across multiple imaging modalities (PET/CT, contrast-enhanced CT, and abdominal MRI), with marked clinical improvement in pain, energy levels, and quality of life, enabling the patient to fully resume physical activity.

Single-patient case report. A 58-year-old woman with therapy-refractory grade G3 neuroendocrine pancreatic tumor underwent [68Ga]Ga-DOTA-LM3 PET/CT for receptor imaging, followed by three cycles of concurrent [177Lu]Lu-DOTA-LM3 and [225Ac]Ac-DOTA-LM3 TANDEM-PRRT. Response was assessed via PET/CT, contrast-enhanced CT of the chest-abdomen-pelvis, and abdominal MRI.

This case demonstrates the potential of TANDEM-PRRT using a somatostatin receptor antagonist (LM3) in a patient who had already exhausted multiple standard treatments including conventional PRRT with [177Lu]Lu-DOTATATE, chemotherapy, targeted therapy (Everolimus), somatostatin analogs, and liver embolization. The dramatic response suggests that receptor antagonists may bind to more receptor sites than traditional agonists, and that combining lutetium-177 with actinium-225 in a tandem approach could offer a powerful salvage option for patients with no remaining standard therapies.

Standard peptide receptor radionuclide therapy (PRRT) with [177Lu]Lu-DOTATATE is already an established treatment for neuroendocrine tumors, but some patients stop responding. This case explores two innovations simultaneously: using a receptor antagonist (LM3) instead of the standard agonist, and combining two radioisotopes in a tandem approach. If these results hold in larger studies, TANDEM-PRRT with receptor antagonists could become an important salvage therapy for patients who have exhausted conventional options.

As a single case report, these results cannot be generalized to other patients. There is no control comparison, and long-term durability of the response is not described. The specific doses and intervals between TANDEM-PRRT cycles are not detailed in the abstract.