RT Journal Article
SR Electronic
T1 Neutron-Activatable Holmium-Containing Mesoporous Silica Nanoparticles as a Potential Radionuclide Therapeutic Agent for Ovarian Cancer
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 111
OP 116
DO 10.2967/jnumed.112.106609
VO 54
IS 1
A1 Anthony J. Di Pasqua
A1 Hong Yuan
A1 Younjee Chung
A1 Jin-Ki Kim
A1 James E. Huckle
A1 Chenxi Li
A1 Matthew Sadgrove
A1 Thanh Huyen Tran
A1 Michael Jay
A1 Xiuling Lu
YR 2013
UL http://jnm.snmjournals.org/content/54/1/111.abstract
AB 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.