Tumor accumulation of neutron-activatable holmium-containing mesoporous silica nanoparticles in an orthotopic non-small cell lung cancer mouse model

Abstract

Mesoporous silica MCM-41 nanoparticles containing the stable isotope holmium-165 (165Ho) were prepared by exposing the approximately 400 nm particles to an aqueous solution of 165Ho acetylacetonate for 24 h at room temperature; the obtained solid was subsequently irradiated in a PULSTAR nuclear reactor (reactor power = 1 MW; thermal neutron flux of approximately 5.5 or 7.7 × 1012 n/cm2s) to produce holmium-166-containing mesoporous silica (166Ho-MCM-41) nanoparticles (20.8 ± 1.9% w/w 166Ho). The 166Ho-MCM-41 nanoparticles were administered intravenously (i.v.) to orthotopic non-small cell lung cancer A549-luciferase tumor-bearing mice. After 24 h, 4.5 ± 3.9% initial dose per gram (ID/g) of tissue was detected in tumors and after 1 week, this value increased to 58.8 ± 34.7% ID/g. These results demonstrate that mesoporous silica MCM-41 nanoparticles can deliver significant amounts of a therapeutic radionuclide to tumors after i.v. injection. © 2012 Elsevier B.V. All rights reserved.