A vertex-differentiated icosahedral closo-B-12(2-) core was utilized to construct a alpha(v)beta(3) integrin receptor-targeted (via cRGD peptide) high payload MRI contrast agent (CA-12) carrying 11 copies of Gd3+-DOTA chelates attached to the closo-B-12(2-) surface via suitable linkers. The resulting polyfunctional MRI contrast agent possessed a higher relaxivity value per-Gd compared to Omniscan, a small molecular contrast agent commonly used in clinical settings. The alpha(v)beta(3) integrin receptor specificity of CA-12 was confirmed via in vitro cellular binding experiments and in vivo MRI of mice bearing human PC-3 prostate cancer xenografts. Integrin alpha(v)beta(3)-positive MDA-MB-231 cells exhibited 300% higher uptake of CA-12 than alpha(v)beta(3)-negative T47D cells. Serial T1-weighted MRI showed superior contrast enhancement of tumors by CA-12 compared to both a nontargeted 12-fold Gd3+-DOTA closomer control (CA-7) and Omniscan. Contrast enhancement by CA-12 persisted for 4 h postinjection, and subsequent enhancement of kidney tissue indicated a renal elimination route similar to Omniscan. No toxic effects of CA-12 were apparent in any mice for up to 24 h postinjection. Post-mortem ICP-OES analysis at 24 h detected no residual Gd in any of the tissue samples analyzed.