Neutron-activatable holmium-containing mesoporous silica nanoparticles as a potential radionuclide therapeutic agent for ovarian cancer.

Abstract

UNLABELLED:

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.

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.

• Authors: Anthony J Di Pasqua, Hong Yuan, Younjee Chung, Jin-Ki Kim, James E Huckle, Chenxi Li, Matthew Sadgrove, Thanh Huyen Tran, Michael Jay, Xiuling Lu
• Journal: Journal of nuclear medicine : official publication, Society of Nuclear Medicine (J Nucl Med) Vol. 54 Issue 1 Pg. 111-6 (Jan 2013) ISSN: 1535-5667 [Electronic] United States
• PMID: 23100452 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Hydroxybutyrates
• MCM-41
• Organometallic Compounds
• Pentanones
• Radioisotopes
• acetyl acetonate
• Silicon Dioxide
• Holmium

Topics

• Animals
• Cell Line, Tumor
• Female
• Gamma Rays
• Holmium (chemistry)
• Humans
• Hydrophobic and Hydrophilic Interactions
• Hydroxybutyrates (chemistry)
• Mice
• Nanoparticles (chemistry, therapeutic use)
• Neutrons
• Organometallic Compounds (chemistry)
• Ovarian Neoplasms (pathology, radiotherapy)
• Pentanones (chemistry)
• Porosity
• Radioisotopes (therapeutic use)
• Silicon Dioxide (chemistry)