Effective encapsulation of a new cationic gadolinium chelate into apoferritin and its evaluation as an MRI contrast...

Gd-Me(2)DO2A with a T(1) proton relaxivity twice as high as that of commercial Gd-DOTA was newly designed and synthesized. Me(2)DO2A kept its high association property with gadolinium ions (Gd(3+)), and the Gd-Me(2)DO2A was efficiently encapsulated into the apoferritin cavity to further enhance the T(1) relaxivity as much as 10-fold higher than Gd-DOTA on a Gd basis. The high T(1) relaxivity was attained by (i) increased accessibility of water molecules to Gd(3+) ions in the chelate and (ii) macromolecular effect of the encapsulation. By the surface modification of apoferritin with dextran, in vivo blood clearance time of apoferritin could be prolonged. Magnetic resonance imaging of tumor-bearing mice showed that the apoferritin contrast agent accomplished tumor detection effectively as a bright signal as a result of the enhanced permeation and retention effect. Single-dose toxicity test showed no serious side effects. The apoferritin-encapsulated Gd is therefore a possible candidate for a new magnetic resonance imaging contrast agent.