A peptide targeted contrast agent specific to fibrin-fibronectin complexes for cancer molecular imaging with MRI.

Abstract

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.

• Authors: Furong Ye, Xueming Wu, Eun-Kee Jeong, Zhanjun Jia, Tianxin Yang, Denis Parker, Zheng-Rong Lu
• Journal: Bioconjugate chemistry (Bioconjug Chem) Vol. 19 Issue 12 Pg. 2300-3 (Dec 2008) ISSN: 1520-4812 [Electronic] United States
• PMID: 19053180 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Contrast Media
• Fibronectins
• Peptides, Cyclic
• Fibrin
• Gadolinium DTPA

Topics

• Amino Acid Sequence
• Animals
• Cell Line, Tumor
• Contrast Media (chemical synthesis, chemistry, metabolism)
• Fibrin (metabolism)
• Fibronectins (metabolism)
• Gadolinium DTPA (chemistry)
• Humans
• Magnetic Resonance Imaging
• Mice
• Neoplasms (diagnosis, metabolism, pathology)
• Peptides, Cyclic (chemical synthesis, chemistry, metabolism)