Encapsulated or amphiphilic liposomal Fe(III) coordination complexes for MRI studies of tumor uptake and clearance

Abstract

Liposomes containing high-spin Fe(III) coordination complexes were prepared towards the production of MRI probes with improved relaxivity and rapid pharmacokinetic clearance in mice. The amphiphilic Fe(III) complexes were anchored into the liposome with two alkyl chains to give a coordination sphere containing mixed amide hydroxypropyl pendant groups. Three types of MRI probes were prepared including those with intraliposomal Fe(III) complex (LipoA) alone, amphiphilic Fe(III) complex (LipoB) or both intraliposomal and amphiphilic complex (LipoC). Water proton relaxivities r1 and r2 were measured and compared to a small molecule macrocyclic Fe(III) complex containing similar donor groups. Liposomes with amphiphilic Fe(III) complex (LipoB) have a per particle relaxivity of 37,000 and a per iron relaxivity of 2.6 mM-1s-1 in solutions with pH 7.2, 34 C at 1.4 T. Liposomes containing both amphiphilic and intraliposomal Fe(III) complexes (lipoC) have reduced per iron relaxivity of 0.8 mM-1s-1 in solution consistent with quenching of the interior Fe(III) complex relaxivity and per particle relaxivity of 42 ,000 mM-1s-1. Liposomes containing only encapsulated Fe(III) complex have a lower relaxivity of 0.46 mM-1s-1 per iron complex. Studies show that lipoB and lipoC produce enhanced signal in the CT26 tumors of BALB/c mice. However, the biodistribution and clearance of the liposomal nanoparticles differs greatly. LipoB is a blood pool agent with a long circulation time whereas lipoC is cleared more rapidly through both renal and hepatobiliary pathways.