1008130-06-0Relevant articles and documents
Imatinib analogs as potential agents for PET imaging of Bcr-Abl and c-KIT expression at a kinase level
Peng, Zhenghong,Maxwell, David S.,Sun, Duoli,Bhanu Prasad, Basvoju A.,Pal, Ashutosh,Wang, Shimei,Balatoni, Julius,Ghosh, Pradip,Lim, Seok T.,Volgin, Andrei,Shavrin, Aleksander,Alauddin, Mian M.,Gelovani, Juri G.,Bornmann, William G.
, p. 623 - 632 (2014)
We synthesized two series of imatinib mesylate (STI-571) analogs to develop a Bcr-Abl and c-KIT receptor-specific labeling agent for positron emission tomography (PET) imaging to measure Bcr-Abl and c-KIT expression levels in a mouse model. The methods of molecular modeling, synthesis of STI-571 and its analogs, in vitro kinase assays, and radiolabeling are described. Molecular modeling revealed that these analogs bind the same Bcr-Abl and c-KIT binding sites as those bound by STI-571. The analogs potently inhibit the tyrosine kinase activity of Bcr-Abl and c-KIT, similarly to STI-571. [ 18F]-labeled STI-571 was prepared with high specific activity (75 GBq/μmol) by nucleophilic displacement and an average radiochemical yield of 12%. [131I]-labeled STI-571 was prepared with high purity (>95%) and an average radiochemical yield of 23%. The uptake rates of [ 18F]-STI-571 in K562 cells expressing Abl and in U87WT cells overexpressing c-KIT were significantly higher than those in the U87 cell and could be inhibited by STI-71 (confirming the specificity of uptake). PET scans of K562 and U87WT tumor-bearing mice with [18F]-STI-571 as a contrast agent showed visible tumor uptake and tumor-to-non-target contrast.
