RRx-001 Oxidation of Redox Sensitive Protein Thiols in Tumors Measured by Gd-LC7-SH Enhanced MRI In Preclinical Tumor Models
Natarajan Raghunand 1 , Jan Scicinski 2 , Bryan Oronsky 2 , Bhumasamudram Jagadish 3 , Eugene A Mash 3 , and Ronald L Korn 4
Cancer Imaging & Metabolism, Moffitt Cancer
Center, Tampa, Florida, United States,
Pharmaceuticals, Mountain View, California, United
of Chemistry & Biochemistry, The University of Arizona,
Tucson, Arizona, United States,
Endpoints LLC, Scottsdale, Arizona, United States
We have investigated the kinetics of T1-shortening
produced in 3 pre-clinical tumor xenograft models by
Gd-LC7-SH, a DOTA-thiol complex of gadolinium. Mice were
imaged before and at multiple time points following
treatment with RRx-001, a novel anticancer agent that
perturbs tumor redox status. Gd-LC7-SH spontaneously
binds to macromolecular thiol targets following i.v.
administration, producing prolonged shortening of tumor
T1 in untreated animals. Following treatment with
RRx-001 the washout of Gd-LC7-SH from tumors was
markedly faster, consistent with the proposed
glutathione-depleting mechanism of action of the drug.
Use of Gd-LC7-SH-enhanced MRI as a pharmacodynamic
marker of RRx-001 action is discussed.
This abstract and the presentation materials are available to members only;
a login is required.