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RGD targeted poly(L-glutamic acid)-cystamine-(Gd-DO3A) conjugate for detecting angiogenesis biomarker ανβ3 integrin with MR T1 mapping

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Authors: Tianyi Ke, Eun-Kee Jeong, Xuli Wang, Yi Feng, Dennis L Parker, Zheng-Rong Lu

Published Date August 2007 Volume 2007:2(2) Pages 191 - 199
DOI: http://dx.doi.org/10.2147/IJN.S

Tianyi Ke1, Eun-Kee Jeong2, Xuli Wang1, Yi Feng3, Dennis L Parker2, Zheng-Rong Lu1

1Departments of Pharmaceutics and Pharmaceutical Chemistry; 2Radiology and Materials Science and 3Engineering, University of Utah, Salt Lake City, UT, USA

Abstract: Cyclic Arg-Gly-Asp-D-Phe-Lys [c(RGDfK)] targeted poly(L-glutamic acid) (PGA)-(Gd-DO3A) conjugate with a biodegradable cystamine spacer was prepared and evaluated for in vivo detection of an angiogenesis biomarker, ανβ3 integrin, in neoplastic tissues with T1 mapping, a quantitative magnetic resonance imaging (MRI) technique. The binding activity of the c(RGDfK) containing conjugate was investigated using in vitro vitronectin assay with human prostate carcinoma DU145 cell line and Kaposi’s sarcoma SLK cell line. The peptide c(RGDfK) and PGA-cystamine-(Gd-DO3A) conjugate were used as controls. The binding affinity of polymer bound c(RGDfK) was slightly lower than free c(RGDfK) peptide. The RGD targeted conjugate had higher binding affinity to the DU145 cells than the SLK cells, which was consistent to free c(RGDfK). The imaging of ανβ3 integrin with targeted PGA-cystamine-(Gd-DO3A) was evaluated in nude mice bearing DU145 and SLK xenografts at a dose of 5 µmol-Gd/kg. The targeted conjugate demonstrated higher in vivo binding affinity to the DU145 xenografts than the SLK xenografts, resulting in a significant decrease of T1 values of water protons in the periphery of the DU145 tumors as shown in the MR T1 maps. No significant decrease of T1 values was observed in the SLK tumor with the targeted conjugate and in both tumors with the non-targeted conjugate. The targeted polymeric Gd(III) chelate conjugate with a degradable spacer has the potential to be a new paradigm for safe and effective probes in molecular imaging with quantitative MR T1 mapping.

Keywords: MRI contrast agent, ανβ3 integrin, RGD, PGA-cystamine-(Gd-DO3A), MR T1 mapping








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