Self-organized Mn2+-block copolymer complexes and their use for in vivo MR imaging of biological processes

Abstract

Manganese-block copolymer complexes (MnBCs) that contain paramagnetic Mn ions complexed with ionic–nonionic poly(ethylene oxide-b-poly(methacrylate) have been developed for use as a T₁-weighted MRI contrast agent. By encasing Mn ions within ionized polymer matrices, r1 values could be increased by 250–350% in comparison with free Mn ions at relatively high fields of 4.7 to 11.7 T. MnBCs were further manipulated by treatment with NaOH to achieve more stable complexes (iMnBCs). iMnBCs delayed release of Mn²⁺ which could be accelerated by low pH, indeed by cellular uptake via endocytosis into acidic compartments. Both complexes exhibited good T₁ contrast signal enhancement in the liver following intravenous infusion. The contrast was observed in the gallbladder due to the clearance of Mn ions from the liver to the biliary process. iMnBCs, notably, showed a delayed contrast enhancement profile in the gallbladder, which was interpreted to be due to degradation and excretion of Mn²⁺ ions into the gallbladder. Intracortical injection of iMnBCs into the rat brain also led to delayed neuronal transport to the thalamus. The delayed enhancement feature may have benefits for targeting MRI contrast to specific cells and surface receptors that are known to be internalized by endocytosis.