We compared the enhancement effect between a newly synthesized tissue-specific contrast agent, [Gd-DOTA-FPβG], and a commercially available agent, [Gd(DOTA)]−, in a murine model of liver tumor using a clinical magnetic resonance imaging scanner. The colon cancer cell lines with and without β-glucuronidase (βG) expression were implanted into the liver of mice. Self-synthesized gadolinium-based magnetic resonance contrast agent, [Gd(DOTA-FPβG)], was administered to measure enhancement on magnetic resonance images using a commercially available agent, [Gd(DOTA)]−, as control in a clinical 3.0 tesla (T) magnetic resonance scanner. In vivo fluorescence imaging and histopathology of the liver were also performed to compare and correlate with the magnetic resonance studies. The in vivo fluorescence imaging failed to depict a sufficiently intense signal for liver or liver tumor of mice without exposure of the liver following an incision on the abdominal wall. The tissue-specific magnetic resonance agent, [Gd(DOTA-FPβG)], caused significantly stronger enhancement in tumors expressing βG (CT26/mβG-eB7) than in tumors not expressing βG (CT26) (p