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 [¹¹C-methyl]quaternary amine target tracers, N-[¹¹C]methyl-N-[4-(cholest-5-en-3β-yloxycarbonyl)butyl]pyrrolidinium iodide ([¹¹C]4a), N-[¹¹C]methyl-N′-[4-(cholest-5-en-3β-yloxycarbonyl)butyl]imidazolium iodide ([¹¹C]4b), N-[¹¹C]methyl-N-[4-(cholest-5-en-3β-yloxycarbonyl)butyl]piperidinium iodide ([¹¹C]4c), N-[¹¹C]methyl-N-[4-(cholest-5-en-3β-yloxycarbonyl)butyl]-4-methylpiperidinium iodide ([¹¹C]4d), and N-[¹¹C]methyl-N-[4-(cholest-5-en-3β-yloxycarbonyl)butyl]morpholinium iodide ([¹¹C]4e), were prepared from their corresponding tertiary amine precursors with [¹¹C]methyl iodide ([¹¹C]CH₃I) through N-[¹¹C]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 [¹¹C]CO₂, and 111-185 GBq/μmol specific activity at the end of synthesis (EOS).