A MODULAR LYMPHOGRAPHIC MAGNETIC-RESONANCE-IMAGING CONTRAST AGENT - CONTRAST ENHANCEMENT WITH DNA TRANSFECTION POTENTIAL

A gadolinium-chelated liposomal contrast agent has been prepared, and magnetic resonance imaging (MRL) efficacy has been examined by indirec t magnetic resonance lymphography. A lipidic N,N'-dimethylethylenediam ine derivative (4) containing a 10,12-diyne-diacyl domain was treated with DTPA anhydride followed by GdCl3 complexation. The complex was co nfirmed using MALDI spectrometry, An equimolar mixture of the Gd-chela te lipid and a commercially available diyne-PE was formulated as a lip osome suspension and irradiated with UV light prior to imaging experim ents. Sabcutaneous injection of the liposomal gadolinium agent and sub sequent MRI of rabbit axillary and popliteal lymph nodes revealed sign ificant contrast enhancement up to 4 h postinjection. To explore the p ossibility of imaging a DNA transfection event, the gadolinium contras t mixture was formulated with the cationic transfection Lipid DOTAP an d complexed with the reporter gene encoding luciferase. DNA transfecti on studies on the NIH3T3 cell line confirmed the transfection activity of the dual-purpose contrast agent and exemplified the potential towa rd development of an imaging and DNA delivery vehicle.