title: 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 (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)s). 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% ± 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 (18)F-FDG uptake in tumors, which correlated with a marked increase in survival after treatment with approximately 4 MBq of (166)Ho-MSNs.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Center for Nanotechnology in Drug Delivery, Division of Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Di Pasqua
authors.forename: Hong
authors.initials: H
authors.lastname: Yuan
authors.forename: Younjee
authors.initials: Y
authors.lastname: Chung
authors.forename: Jin-Ki
authors.initials: JK
authors.lastname: Kim
authors.forename: James E
authors.initials: JE
authors.lastname: Huckle
authors.forename: Chenxi
authors.initials: C
authors.lastname: Li
authors.forename: Matthew
authors.initials: M
authors.lastname: Sadgrove
authors.forename: Thanh Huyen
authors.initials: TH
authors.lastname: Tran
authors.forename: Michael
authors.initials: M
authors.lastname: Jay
authors.forename: Xiuling
authors.initials: X
authors.lastname: Lu
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D005260:Female; D005720:Gamma Rays; D006695:Holmium / Q000737:chemistry*; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D006885:Hydroxybutyrates / Q000737:chemistry; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry* / Q000627:therapeutic use*; D009502:Neutrons; D009942:Organometallic Compounds / Q000737:chemistry; D010051:Ovarian Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D010422:Pentanones / Q000737:chemistry; D016062:Porosity; D011868:Radioisotopes / Q000627:therapeutic use; D012822:Silicon Dioxide / Q000737:chemistry*
chemical_list: D006885:Hydroxybutyrates; C509968:MCM-41; D009942:Organometallic Compounds; D010422:Pentanones; D011868:Radioisotopes; C049529:acetyl acetonate; D012822:Silicon Dioxide; D006695:Holmium