Free radicals are associated with
glioma tumors. Here, we report on the ability of an anticancer nitrone compound,
OKN-007 [Oklahoma Nitrone 007; a disulfonyl derivative of α-phenyl-tert-butyl nitrone (PBN)] to decrease
free radical levels in F98 rat
gliomas using combined molecular magnetic resonance imaging (mMRI) and immunospin-trapping (IST) methodologies.
Free radicals are trapped with the spin-trapping agent, 5,5-dimethyl-1-pyrroline N-
oxide (DMPO), to form DMPO macromolecule radical adducts, and then further tagged by immunospin trapping by an antibody against DMPO adducts. In this study, we combined mMRI with a
biotin-
Gd-DTPA-albumin-based
contrast agent for signal detection with the specificity of an antibody for DMPO nitrone adducts (anti-DMPO probe), to detect in vivo
free radicals in OKN-007-treated rat F98
gliomas.
OKN-007 was found to significantly decrease (P < 0.05)
free radical levels detected with an anti-DMPO probe in treated animals compared to untreated rats. Immunoelectron microscopy was used with
gold-labeled antibiotin to detect the anti-DMPO probe within the plasma membrane of F98
tumor cells from rats administered anti-DMPO in vivo.
OKN-007 was also found to decrease nuclear factor erythroid 2-related factor 2,
inducible nitric oxide synthase,
3-nitrotyrosine, and
malondialdehyde in ex vivo F98
glioma tissues via immunohistochemistry, as well as decrease
3-nitrotyrosine and
malondialdehyde adducts in vitro in F98 cells via ELISA. The results indicate that
OKN-007 effectively decreases
free radicals associated with
glioma tumor growth. Furthermore, this method can potentially be applied toward other types of
cancers for the in vivo detection of macromolecular
free radicals and the assessment of
antioxidants.