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

Ye F, Wu X, Jeong EK, Jia Z, Yang T, Parker D, Lu ZR - Bioconjug. Chem. (2008)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, and Veterans Affairs Medical Center, Salt Lake City, Utah, USA.

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.

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T1-weighted 2D spin−echo images of mice bearing HT-29 xenografts before contrast and at 10, 30, and 60 min postinjection of CLT1−(Gd-DTPA), Omniscan and competitive mixture. Arrow points to the tumor tissue.
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fig2: T1-weighted 2D spin−echo images of mice bearing HT-29 xenografts before contrast and at 10, 30, and 60 min postinjection of CLT1−(Gd-DTPA), Omniscan and competitive mixture. Arrow points to the tumor tissue.

Mentions: Figure 2 shows the representative axial T1-weighted 2D spin−echo images of the tumor tissues of the mice bearing HT-29 tumor xenografts before and after injection of the contrast agents. Significant enhancement was observed in tumor tissues for CLT1-(Gd-DTPA) 10 min postinjection, and strong enhancement was visible in the tumor tissues at 60 min after injection. For the competitive study, the tumor enhancement with CLT1−(Gd-DTPA) was reduced after the coinjection of free peptide, which indicates that the free peptide recognizes the same binding site within tumor tissue as CLT1−(Gd-DTPA). The control agent Gd(DTPA-BMA) did not show a strong tumor enhancement as compared to CLT1−(Gd-DTPA).


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

Ye F, Wu X, Jeong EK, Jia Z, Yang T, Parker D, Lu ZR - Bioconjug. Chem. (2008)

T1-weighted 2D spin−echo images of mice bearing HT-29 xenografts before contrast and at 10, 30, and 60 min postinjection of CLT1−(Gd-DTPA), Omniscan and competitive mixture. Arrow points to the tumor tissue.
© Copyright Policy - open-access - ccc-price
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2651601&req=5

fig2: T1-weighted 2D spin−echo images of mice bearing HT-29 xenografts before contrast and at 10, 30, and 60 min postinjection of CLT1−(Gd-DTPA), Omniscan and competitive mixture. Arrow points to the tumor tissue.
Mentions: Figure 2 shows the representative axial T1-weighted 2D spin−echo images of the tumor tissues of the mice bearing HT-29 tumor xenografts before and after injection of the contrast agents. Significant enhancement was observed in tumor tissues for CLT1-(Gd-DTPA) 10 min postinjection, and strong enhancement was visible in the tumor tissues at 60 min after injection. For the competitive study, the tumor enhancement with CLT1−(Gd-DTPA) was reduced after the coinjection of free peptide, which indicates that the free peptide recognizes the same binding site within tumor tissue as CLT1−(Gd-DTPA). The control agent Gd(DTPA-BMA) did not show a strong tumor enhancement as compared to CLT1−(Gd-DTPA).

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, and Veterans Affairs Medical Center, Salt Lake City, Utah, USA.

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.

Show MeSH
Related in: MedlinePlus