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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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Related in: MedlinePlus

Plots of CNR versus time in tumor periphery (A) and inner area (B) before contrast and at 1, 10, 30, and 60 min postinjection of CLT1−(Gd-DTPA), Omniscan, and competitive mixture.
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fig3: Plots of CNR versus time in tumor periphery (A) and inner area (B) before contrast and at 1, 10, 30, and 60 min postinjection of CLT1−(Gd-DTPA), Omniscan, and competitive mixture.

Mentions: MR signal intensity was also measured, and the contrast to noise ratio (CNR) in the tumor tissues was calculated as CNR = (SItissue − SImuscle)/SDnoise. Statistical analysis was perform using two-way ANOVA. Figure 3 shows the CNR of the tumor tissue in tumor periphery and inner areas before and at various time points after injecting the contrast agents. CLT1−(Gd-DTPA) showed higher CNR at 10 min after injection in the tumor periphery area and decreased gradually. At the same time, CNR in tumor inner area increased gradually during the period of 60 min postinjection. The CNR in both tumor periphery and inner tissue with Gd(DTPA-BMA) decreased rapidly after it reached the maximum values at 1 min postinjection. The CLT1−(Gd-DTPA) showed significantly higher CNR than the control Gd(DTPA-BMA) in tumor periphery since 10 min postinjection (p < 0.05) and in the tumor inner area since 30 min postinjection (p < 0.05). The results indicate binding and retention of the targeted contrast agent to tumor tissue. The presence of free peptide resulted in significant reduction of CNR in both tumor periphery and inner tumor tissue (p < 0.05) except at the point of 30 min postinjection. The result indicated that the presence of free peptide inhibited the binding of the targeted contrast agent to its target, resulting in decreased contrast enhancement in tumor tissue.


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)

Plots of CNR versus time in tumor periphery (A) and inner area (B) before contrast and at 1, 10, 30, and 60 min postinjection of CLT1−(Gd-DTPA), Omniscan, and competitive mixture.
© Copyright Policy - open-access - ccc-price
Related In: Results  -  Collection

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

fig3: Plots of CNR versus time in tumor periphery (A) and inner area (B) before contrast and at 1, 10, 30, and 60 min postinjection of CLT1−(Gd-DTPA), Omniscan, and competitive mixture.
Mentions: MR signal intensity was also measured, and the contrast to noise ratio (CNR) in the tumor tissues was calculated as CNR = (SItissue − SImuscle)/SDnoise. Statistical analysis was perform using two-way ANOVA. Figure 3 shows the CNR of the tumor tissue in tumor periphery and inner areas before and at various time points after injecting the contrast agents. CLT1−(Gd-DTPA) showed higher CNR at 10 min after injection in the tumor periphery area and decreased gradually. At the same time, CNR in tumor inner area increased gradually during the period of 60 min postinjection. The CNR in both tumor periphery and inner tissue with Gd(DTPA-BMA) decreased rapidly after it reached the maximum values at 1 min postinjection. The CLT1−(Gd-DTPA) showed significantly higher CNR than the control Gd(DTPA-BMA) in tumor periphery since 10 min postinjection (p < 0.05) and in the tumor inner area since 30 min postinjection (p < 0.05). The results indicate binding and retention of the targeted contrast agent to tumor tissue. The presence of free peptide resulted in significant reduction of CNR in both tumor periphery and inner tumor tissue (p < 0.05) except at the point of 30 min postinjection. The result indicated that the presence of free peptide inhibited the binding of the targeted contrast agent to its target, resulting in decreased contrast enhancement in tumor tissue.

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