Neutron-Activatable Holmium-Containing Mesoporous Silica Nanoparticles as a Potential Radionuclide Therapeutic Agent for Ovarian Cancer

Mesoporous silica nanoparticles (MSNs) were explored as a carrier material for the stable isotope ¹⁶⁵Ho and, after neutron capture, its subsequent therapeutic radionuclide, ¹⁶⁶Ho (half-life, 26.8 h), for use in radionuclide therapy of ovarian cancer metastasis. Methods:¹⁶⁵Ho-MSNs were prepared using ¹⁶⁵Ho-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 × 10¹² neutrons/cm²·s). SPECT/CT and tissue biodistribution studies were performed after intraperitoneal administration of ¹⁶⁶Ho-MSNs to SKOV-3 ovarian tumor–bearing mice. Radiotherapeutic efficacy was studied by using PET/CT with ¹⁸F-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 ¹⁶⁶Ho after significant dilution. SPECT/CT images and tissue distribution results revealed that ¹⁶⁶Ho-MSNs accumulated predominantly in tumors (32.8% ± 8.1% injected dose/g after 24 h; 81% ± 7.5% injected dose/g after 1 wk) after intraperitoneal administration. PET/CT images showed reduced ¹⁸F-FDG uptake in tumors, which correlated with a marked increase in survival after treatment with approximately 4 MBq of ¹⁶⁶Ho-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.