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

Abstract

Mesoporous silica nanoparticles (MSNs) were explored as a carrier material for the stable isotope Ho-165 and, after neutron capture, its subsequent therapeutic radionuclide, Ho-166 (half-life, 26.8 h), for use in radionuclide therapy of ovarian cancer metastasis. Methods: Ho-165-MSNs were prepared using Ho-166-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 x 10(12) neutrons/cm(2).s). SPECT/CT and tissue biodistribution studies were performed after intraperitoneal administration of Ho-166-MSNs to SKOV-3 ovarian tumor-bearing mice. Radiotherapeutic efficacy was studied by using PET/CT with F-18-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 Ho-166 after significant dilution. SPECT/CT images and tissue distribution results revealed that Ho-166-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 F-18-FDG uptake in tumors, which correlated with a marked increase in survival after treatment with approximately 4 MBq of Ho-166-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.