Use of DNA Microarray and Small Animal Positron Emission Tomography in Preclinical Drug Evaluation of RAF265, a Novel B-Raf/VEGFR-2 Inhibitor

• DOI: 10.1593/neo.101466
• Publication Date: 2015-04-23T09:01:32Z
• Authors: Jeffrey R. Tseng; Darrin Stuart; Kimberly Aardalen; Angelo Kaplan; Natasha Aziz; Nicholas P. Hughes; Sanjiv S. Gambhir
• Keywords: Tissue microarray

Positron emission tomography (PET) imaging has become a useful tool for assessing early biologic response to cancer therapy and may be particularly in the development of new therapeutics. RAF265, novel B-Raf/vascular endothelial growth factor receptor-2 inhibitor, was evaluated preclinical setting its ability inhibit uptake PET tracers A375M(B-Raf(V600E)) human melanoma cell line. RAF265 inhibited 2-deoxy-2-[(18)F]fluoro-d-glucose (FDG) accumulation culture at 28 hours dose-dependent manner. also FDG tumor xenografts after 1 day drug treatment. This decrease persisted remaining 2 weeks DNA microarray analysis treated revealed significantly decreased expression genes regulating glucose thymidine metabolism changes apoptotic genes, suggesting that FDG, 3-deoxy-3-[(18)F]fluorothymidine, annexin V could serve as potential biomarkers monitoring. We concluded is highly efficacious this xenograft model decreases measured by analysis, assays, small animal scans Our results support use clinical trials with assess response. studies used complementary technologies development. allows effects on multiple pathways linked can suggest corresponding further