Mesoporous silica nanoparticles (MSNs) were explored as a carrier material for the stable isotope 165 Ho and, after neutron capture, its subsequent therapeutic radionuclide, 166 Ho (half-life, 26.8 h), for use in radionuclide therapy of ovarian cancer metastasis. Methods: 165 Ho-MSNs were prepared using 165 Ho-acetylacetonate and MCM-41 silica particles, and stability was determined after irradiation in a nuclear reactor (reactor power, 1 MW; thermal neutron flux of approximately 5.5 · 10 12 neutrons/cm 2 Ás). SPECT/ CT and tissue biodistribution studies were performed after intraperitoneal administration of 166 Ho-MSNs to SKOV-3 ovarian tumor-bearing mice. Radiotherapeutic efficacy was studied by using PET/CT with 18 F-FDG to determine tumor volume and by monitoring survival. Results: The holmium-MSNs were able to withstand long irradiation times in a nuclear reactor and did not release 166 Ho after significant dilution. SPECT/CT images and tissue distribution results revealed that 166 Ho-MSNs accumulated predominantly in tumors (32.8% 6 8.1% injected dose/g after 24 h; 81% 6 7.5% injected dose/g after 1 wk) after intraperitoneal administration. PET/CT images showed reduced 18 F-FDG uptake in tumors, which correlated with a marked increase in survival after treatment with approximately 4 MBq of 166 Ho-MSNs. Conclusion: The retention of holmium in nanoparticles during irradiation and in vivo after intraperitoneal administration as well as their efficacy in extending survival in tumor-bearing mice underscores their potential as a radiotherapeutic agent for ovarian cancer metastasis.