Multiparametric assessment of the anti-glioma properties of OKN007 by magnetic resonance imaging.
OBJECTIVE
To demonstrate that OKN007, a disulfonyl derivative of phenyl-tert-butyl nitrone (PBN), has anti-glioma activity in the clinically relevant C6 rat glioma model using multi-parametric magnetic resonance imaging.


METHODS
Twenty-one rats were intracerebrally implanted with C6 cells and administered OKN007 or kept as controls. Animals were monitored with MRI at 7 Tesla (T), using morphologic, diffusion-weighted and perfusion imaging, followed by histology and Western blots of angiogenesis and inflammatory markers.


RESULTS
OKN007 was found to decrease tumor volumes and increase survival. The glioma tissues of OKN007-treated rats were found to have longitudinal apparent diffusion coefficients (ADC(z)) of 0.76 +/- 0.06 x 10(-3) mm(2)/s, similar to the contralateral tissue and significantly smaller than untreated gliomas (0.97 +/- 0.13 x 10(-3) mm(2)/s). They had higher perfusion rates (66 +/- 4 mL/100 g.min) than untreated gliomas (26 +/- 7 mL/100 g.min). All examined molecular markers were decreased in OKN007-treated rat gliomas, compared with elevated levels in untreated rats.


CONCLUSIONS
MRI assessment was successfully used to monitor a decrease in tumor growth, and corresponding alterations in ADC and perfusion rates in rat C6 gliomas treated with the anti-glioma agent, OKN007.
Garteiser
Philippe
P
Advanced Magnetic Resonance Center, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma 73104, USA.
Doblas
Sabrina
S
Watanabe
Yasuko
Y
Saunders
Debbie
D
Hoyle
Jessica
J
Lerner
Megan
M
He
Ting
T
Floyd
Robert A
RA
Towner
Rheal A
RA
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001557:Benzenesulfonates / Q000627:therapeutic use*; D001921:Brain / Q000473:pathology; D045744:Cell Line, Tumor; D004058:Diffusion; D004195:Disease Models, Animal; D004354:Drug Screening Assays, Antitumor; D005910:Glioma / Q000188:drug therapy*; D007097:Imines / Q000627:therapeutic use*; D007249:Inflammation; D008279:Magnetic Resonance Imaging / Q000379:methods*; D009368:Neoplasm Transplantation; D010477:Perfusion; D051381:Rats; D013997:Time Factors; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D001557:Benzenesulfonates; D007097:Imines; C552724:OKN 007