An intravascular MRI contrast agent Gd(DO3A-Lys), Gadolinium(III) (2,2',2″-(10-(3-(5-benzamido-6-methoxy-6-oxohexylamino)-3-oxopropyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl)triacetate), has been studied for tumor angiography based on its high relaxivity and long blood half-life. The preparation procedures of the contrast agent have been modified in order to achieve higher yield and improve the synthetic reproducibility. High relaxivity of Gd(DO3A-Lys) has been confirmed by measurements at 3T, 7T and 9.4T magnetic fields. The relaxivity-dependent albumin binding study indicated that Gd(DO3A-Lys) partially bound to albumin protein. Invitro cell viability in HK2 cell indicated low cytotoxicity of Gd(DO3A-Lys) up to 1.2mm [Gd] concentration. Invivo toxicity studies demonstrated no toxicity of Gd(DO3A-Lys) on kidney tissues up to 0.2mm [Gd]. While the toxicity on liver tissue was not observed at low dosage (1.0mm [Gd]), Gd(DO3A-Lys) cause certain damage on hepatic tissue at high dosage (2.0mm [Gd]). The DO3A-Lys has been labeled with 68Ga radioisotope for biodistribution studies. 68Ga(DO3A-Lys) has high uptake in both HT1080 and U87MG xenograft tumors, and has high accumulation in blood. Contrast-enhanced MR angiography (CE-MRA) in mice bearing U87MG xenograft tumor demonstrated that Gd(DO3A-Lys) could enhance vascular microenvironment around the tumor, and displays promising characteristics of an MRI contrast agent for tumor angiography. © 2013 Elsevier Ltd.
CITATION STYLE
Yang, C. T., Chandrasekharan, P., He, T., Poh, Z., Raju, A., Chuang, K. H., & Robins, E. G. (2014). An intravascular MRI contrast agent based on Gd(DO3A-Lys) for tumor angiography. Biomaterials, 35(1), 327–336. https://doi.org/10.1016/j.biomaterials.2013.10.006
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