TITLE:
Enhancement of Tumor Regression by Coulomb Nanoradiator Effect in Proton Treatment of Iron-Oxide Nanoparticle-Loaded Orthotopic Rat Glioma Model: Implication of Novel Particle Induced Radiation Therapy
AUTHORS:
Seung-Jun Seo, Jae-Kun Jeon, Eun-Ju Jeong, Won-Seok Chang, Gi-Hwan Choi, Jong-Ki Kim
KEYWORDS:
Proton Therapy; Iron Oxide Nanoparticles; Coulomb Nanoradiator; Malignant Glioma
JOURNAL NAME:
Journal of Cancer Therapy,
Vol.4 No.11A,
December
12,
2013
ABSTRACT:
Background: Proton-impact metallic
nanoparticles, inducing low-energy electrons emission and characteristic X-rays
termed as Coulomb nanoradiator effect (CNR), are known to produce therapeutic enhancement in proton treatment on
experimental tumors. The purpose of this pilot study was to investigate the effect
of CNR-based dose enhancement on tumor growth
inhibition in an iron-oxide nanoparticle (FeONP)-loaded orthotopic rat glioma
model. Methods: Proton-induced CNR
was exploited to treat glioma-bearing SD rat loaded with FeONP by either fully-absorbed
single pristine Bragg peak (APBP) or spread-out Bragg peak (SOBP) 45-MeV proton
beam. A selected number of rats were examined by MRI before and after treatment
to obtain the size and position information for adjusting irradiation field.
Tumor regression assay was performed by histological analysis of residual tumor
in the sacrificed rats 7 days after treatment. The results of CNR-treated
groups were compared with the proton alone control. Results: Intravenous injection of FeONP (300 mg/kg) elevated the tumor
concentration of iron up to 37 μg of Fe/g
tissue, with a tumor-to-normal ratio of 5, 24 hours after injection. The group
receiving FeONP and proton beam showed 65% - 79% smaller tumor volume dose-dependently compared
with the proton alone group. The rats receiving FeONP and controlled irradiation
field by MR imaging demonstrated more than 95% - 99% tumor regression compared with MRI-determined
initial tumor size. Conclusions: Proton-impact
FeONP produced therapeutic enhancement compared with proton alone in an
orthotopic rat glioma model at a selected temporal point after treatment.
Single BP proton beam could induce CNR- based dose enhancement and produce enhanced tumor regression that was
comparable to SOBP treatment despite inhomogeneous tumor dose in the
APBP-treated tumor. These results may suggest emergence of novel Particle
Induced Radiation Therapy (PIRT) on malignant glioma.