Magnetic resonance imaging of RRx-001 pharmacodynamics in preclinical tumors
Author
Raghunand, NatarajanScicinski, Jan
Guntle, Gerald P.
Jagadish, Bhumasamudram
Mash, Eugene A.
Bruckheimer, Elizabeth
Oronsky, Bryan
Korn, Ronald L.
Affiliation
Univ Arizona, Arizona Canc CtrUniv Arizona, Dept Chem & Biochem
Issue Date
2017-06-13
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IMPACT JOURNALS LLCCitation
Magnetic resonance imaging of RRx-001 pharmacodynamics in preclinical tumors 2017, 8 (60) OncotargetJournal
OncotargetRights
© Raghunand et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0).Collection Information
This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.Abstract
RRx-001 is an anticancer agent that subjects cancer cells to reactive oxygen/nitrogen species (ROS/RNS) and acts as an epigenetic modifier. We have used a thiol-bearing MRI contrast agent, Gd-LC7-SH, to investigate the pharmacodynamics of RRx-001 in CHP-100 Ewing's Sarcoma, HT-29 colorectal carcinoma, and PANC-1 pancreatic carcinoma xenografts in SCID mice. Binding of Gd-LC7-SH to the Cys34 residue on plasma albumin prolongs retention in the tumor microenvironment and increases tumor enhancement on MRI. Mice were imaged by MRI and in vivo T1 maps acquired 50 min (T1(50 min)) after injection of 0.05 mmol/kg Gd-LC7-SH (i.v.) at baseline and 1, 24, and 72 h post-treatment with 10 mg/kg RRx-001 (i.v.). Consistent with an indirect thiol-modifying activity of RRx-001, tumor T150 min at 1 h post-drug was significantly longer than pre-drug tumor T150 min in all three tumor models, with the T150 min remaining significantly longer than baseline through 72 h post-drug in the HT-29 and PANC-1 tumors. The T150 min of CHP-100 tumors recovered to baseline by 24 h post-drug, suggesting a robust anti-oxidant response to the RRx-001 challenge that was presaged by a marked increase in perfusion at 1 h post-drug measured by DCE-MRI. MRI enhanced with Gd-LC7-SH provides a mechanistically rational biomarker of RRx-001 pharmacodynamics.ISSN
1949-2553PubMed ID
29254266Version
Final published versionSponsors
EpicentRx; National Institutes of Health [R01-CA118359, P30-CA023074]Additional Links
http://www.oncotarget.com/fulltext/18455ae974a485f413a2113503eed53cd6c53
10.18632/oncotarget.18455
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Except where otherwise noted, this item's license is described as © Raghunand et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0).
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