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

Abstract

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]CH 3I) 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]CO 2, and 111–185 GBq/μmol specific activity at the end of synthesis (EOS).