Facile synthesis of carbon-11-labeled cholesterol-based cationic lipids as new potential PET probes for imaging of gene delivery in cancer

Gene therapy based on gene delivery is a promising strategy for the treatment of various human diseases such as cancer. Cationic lipids represent one of the important synthetic gene delivery systems. There is a great interest in imaging of gene therapy using the biomedical imaging technique positron emission tomography (PET). Carbon-11-labeled cholesterol-based cationic lipids were first designed and synthesized as new potential PET probes for imaging of gene delivery in cancer. The [C-11-methyl]quaternary amine target tracers, N-[C-11]methyl-N-[4-(cholest-5-en-3 beta-yloxycarbonyl)butyl]pyrrolidum iodide ([C-11]4a), N-[C-11]methyl-N'-[4-(cholest-5-en-3 beta-yloxycarbonyl)butyl]imidazolium iodide ([C-11]4b), N-[C-11]methyl-N'-[4-(cholest-5-en-3 beta-yloxycarbonyl)butyl]piperidinium iodide ([C-11]4c), N-[C-11]methyl-N-[4-(cholest-5-en-3 beta-yloxycarbonyl)butyl]-4-methylpiperidinium iodide ([C-11]4d), and N-[C-11]methyl-N-[4-(cholest-5-en-3 beta-yloxycarbonyl)butyl]morpholinium iodide ([C-11]4e), were prepared from their corresponding tertiary amine precursors with [C-11]methyl iodide ([C-11]CH3I) through N-[C-11]methylation and isolated by a simplified solid-phase extraction (SPE) method using a Silica Sep-Pak cartridge in 50-60% radiochemical yields decay corrected to end-of-bombardment (EOB), based on [C-11]CO2, and 111-185 GBq/mu mol specific activity at the end of synthesis (EOS). (C) 2010 Elsevier Inc. All rights reserved.