Novel therapy for gastric cancer peritoneal dissemination using genetically modified dental pulp cells and astatine-211

Peritoneal dissemination of gastric cancer represents a terminal stage with limited therapeutic options and a five-year survival rate below 10%. To develop a more effective treatment, we established a novel α-particle–based approach using genetically engineered human dental pulp stem cells (DPCs) expressing the sodium/iodide symporter (NIS) to deliver astatine-211 (At-211) directly to tumor sites. DPCs, isolated and expanded under differentiation-suppressive conditions, showed strong tumor-homing ability when injected intraperitoneally into a mouse model of gastric cancer dissemination. Fluorescent imaging and histological analysis confirmed selective accumulation of DPCs within tumor lesions through CXCR4/SDF-1–mediated chemotaxis. Introduction of the NIS gene markedly increased SLC5A5 expression and enabled efficient uptake of At-211. High-resolution α-particle imaging visualized α-ray emission specifically from NIS-DPCs, confirming intracellular retention of the radionuclide. In vivo, sequential administration of NIS-DPCs followed by Na[At-211] led to pronounced regression of peritoneal tumors and significant survival extension compared with controls. The therapeutic mechanism involves three coordinated steps: tumor-directed migration of NIS-DPCs, At-211 uptake via NIS transporters, and localized α-particle–mediated cytotoxicity. This study introduces a novel concept of cell-based α-radiotherapy integrating regenerative and nuclear medicine. Given the established clinical safety of DPCs in humans (J-REPAIR, jRCT1080224505), this NIS-DPC platform offers a promising strategy for precise, short-range irradiation of disseminated gastric cancer and potentially other intractable malignancies.