Magnetic resonance imaging of RRx-001 pharmacodynamics in preclinical tumors.

摘要: RRx-001 is an anticancer agent that subjects cancer cells to reactive oxygen/nitrogen species (ROS/RNS) and acts as epigenetic modifier. We have used a thiol-bearing MRI contrast agent, Gd-LC7-SH, investigate the pharmacodynamics of in CHP-100 Ewing's Sarcoma, HT-29 colorectal carcinoma, PANC-1 pancreatic carcinoma xenografts SCID mice. Binding Gd-LC7-SH Cys34 residue on plasma albumin prolongs retention tumor microenvironment increases enhancement MRI. Mice were imaged by vivo T1 maps acquired 50 min (T150 min) after injection 0.05 mmol/kg (i.v.) at baseline 1, 24, 72 h post-treatment with 10 mg/kg (i.v.). Consistent indirect thiol-modifying activity RRx-001, T150 1 post-drug was significantly longer than pre-drug all three models, remaining through tumors. The tumors recovered 24 post-drug, suggesting robust anti-oxidant response challenge presaged marked increase perfusion measured DCE-MRI. enhanced provides mechanistically rational biomarker pharmacodynamics.