A Peptide Targeted Contrast Agent Specific to Fibrin-Fibronectin Complexes for Cancer Molecular Imaging with MRI

[Image: see text] A peptide targeted contrast agent, CLT1-(Gd-DTPA), was synthesized for molecular imaging of fibronectin−fibrin complexes in tumor tissue with magnetic resonance imaging (MRI). The T(1) and T(2) relaxivities of CLT1-(Gd-DTPA) were 4.22 and 4.45 mM(−1) s(−1) at 3 T, respectively. The targeted contrast agent specifically bound to tumor tissue and resulted in significant tumor contrast enhancement at a dose of 0.1 mmol Gd/kg for at least 60 min in mice bearing HT-29 human colon carcinoma xenografts as shown in dynamic MR images. In contrast, a control nontargeted contrast agent, Gd(DTPA-BMA), was cleared rapidly with little tumor enhancement 60 min postinjection. Tumor enhancement with CLT1-(Gd-DTPA) was significantly reduced after coinjection with a 3-fold excess of free CLT1 peptide. The preliminary study has shown that CLT1-(Gd-DTPA) can specifically bind to the fibrin−fibronectin complexes in tumor tissues, resulting in significant tumor enhancement. The targeted contrast agent has a potential for cancer molecular imaging with MRI.