10.1016/j.bmc.2013.10.040
The research focused on the synthesis and evaluation of imatinib mesylate (STI-571) analogs as potential agents for PET imaging of Bcr-Abl and c-KIT expression at the kinase level. The study involved molecular modeling to predict binding configurations, followed by the synthesis of STI-571 and its analogs using various reactants such as 2-methyl-5-nitroaniline, cyanamide, and 3-acetylpyridine derivatives. Radiolabeling with [18F] and [131I] was performed to prepare PET imaging agents. In vitro kinase assays were conducted to assess the potency of the analogs in inhibiting Bcr-Abl and c-KIT kinase activities. The uptake rates of [18F]-STI-571 in K562 cells (expressing Abl) and U87WT cells (overexpressing c-KIT) were measured and compared with those in U87 cells. PET scans were conducted on tumor-bearing mice to visualize tumor uptake and contrast. The research utilized various analytical techniques, including HPLC, MS, NMR, and radio-TLC, to monitor reactions, assess radiochemical purity, and characterize compounds. The results showed that the [18F]-STI-571 analog could serve as a marker for sensitivity to Bcr-Abl and c-KIT inhibitors, potentially aiding in patient selection for targeted therapies.
