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 T1 and T2 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.

Phage display and molecular imaging: expanding fields of vision in living subjects

“…Studies in mice strongly indicated that these peptides recognize fibrin-fibrinogen complexes formed by clotting plasma proteins that leaked into the extravascular space in tumors and other lesions. In a preliminary MRI imaging study, the CLT1 peptide was conjugated at the N-terminus with a chelating group for labeling with gadolinium and used to image fibronectin-fibrin complexes within mice bearing HT-29 human colon carcinoma xenografts (Ye et al 2008). …”

In vitro assessment of the dual-targeting behavior of a peptide-based magnetic resonance imaging contrast agent

“…Researchers can design and expediently synthesize the corresponding peptide to meet custom medical purposes. The specific binding of functional peptides to their receptors facilitates the research of targeting contrast agents (7,8).…”

CMR2009: 7.03: Evaluation of a fibrin binding gadolinium chelate peptide tetramer in a brain glioma model

“…In research on tissue-specific contrast agents of porphyrin and nonporphyrin species, necrosis avidity has been recognized as a natural phenomenon exploitable for both diagnostic and therapeutic utilities (1). Anticancer therapies with vascular disrupting agents (VDAs) (2,3) or radiofrequency ablation (RFA) (4) can noninvasively or minimum-invasively induce tumor necrosis but often leave viable residues behind, leading to failure in cancer cure.…”