title: Preparation of polymer-based magnetic resonance imaging contrast agent to visualize therapeutic angiogenesis.
abstract: The objective of this study was to design and prepare a new contrast agent of magnetic resonance (MR) imaging for the evaluation of therapeutic angiogenesis. Diethylenetriaminepentaacetic acid (DTPA) residue of a chelator was chemically introduced to dextran with a molecular weight of 74,000 (dextran-DTPA). Cyclic peptide containing an arginine-glycine-aspartic acid (RGD) sequence (cyclic RGD) with an inherent affinity for the α(v)β(3) integrin was then introduced to dextran-DTPA (Cyclic RGD-dextran-DTPA). Gd(3+) was added to cyclic RGD-dextran-DTPA to prepare a dextran-based MR contrast agent (Cyclic RGD-dextran-DTPA-Gd). Cyclic RGD-dextran-DTPA-Gd had affinity for cells expressing the α(v)β(3) integrin and showed a higher longitudinal relaxivity compared with DTPA-Gd of an MR contrast agent clinically used. Right femoral, external iliac, and deep femoral and circumflex arteries and veins were surgically ligated to prepare a mouse model of hindlimb ischemia. A laser Doppler analysis and histological evaluation confirmed that hindlimb ischemia healed naturally and was accompanied by angiogenesis, while α(v)β(3) integrin was expressed in the ischemic-angiogenic region without any treatment. Mice at 7 days after vascular ligation were used as an angiogenesis model. When intravenously injected into mice with hindlimb ischemia, cyclic RGD-dextran-DTPA accumulated in the ischemic-angiogenic region and showed the MR ability to detect the ischemic-angiogenic region. It is concluded that cyclic RGD-dextran-DTPA-Gd is a promising material for evaluation of therapeutic angiogenesis.
authors: Department of Biomaterials, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan.
authors: Jun-ichiro
authors: J
authors: Jo
authors: Xue
authors: X
authors: Lin
authors: Teppei
authors: T
authors: Nakahara
authors: Ichio
authors: I
authors: Aoki
authors: Tsuneo
authors: T
authors: Saga
authors: Yasuhiko
authors: Y
authors: Tabata
mesh_terms: D000818:Animals; D003287:Contrast Media / Q000138:chemical synthesis*; D003911:Dextrans / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry; D019786:Gadolinium DTPA; D007089:Image Enhancement / Q000379:methods; D007511:Ischemia / Q000150:complications / Q000473:pathology*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009389:Neovascularization, Pathologic / Q000209:etiology / Q000473:pathology*; D009842:Oligopeptides
chemical_list: D003287:Contrast Media; D003911:Dextrans; D004337:Drug Carriers; D009842:Oligopeptides; C047981:arginyl-glycyl-aspartic acid; D019786:Gadolinium DTPA