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An intravascular MRI contrast agent based on Gd(DO3A-Lys) for tumor angiography

Author:
Yang, Chang-Tong, Chandrasekharan, Prashant, He, Tao, Poh, Zihan, Raju, Anandhkumar, Chuang, Kai-Hsiang, Robins, Edward G.
Source:
Biomaterials 2014 v.35 no.1 pp. 327-336
ISSN:
0142-9612
Subject:
albumins, angiography, blood, cell viability, cytotoxicity, gadolinium, half life, kidneys, liver, magnetic fields, magnetic resonance imaging, mice, neoplasms, radionuclides, tissues, toxicity testing
Abstract:
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 3 T, 7 T and 9.4 T magnetic fields. The relaxivity-dependent albumin binding study indicated that Gd(DO3A-Lys) partially bound to albumin protein. In vitro cell viability in HK2 cell indicated low cytotoxicity of Gd(DO3A-Lys) up to 1.2 mm [Gd] concentration. In vivo toxicity studies demonstrated no toxicity of Gd(DO3A-Lys) on kidney tissues up to 0.2 mm [Gd]. While the toxicity on liver tissue was not observed at low dosage (1.0 mm [Gd]), Gd(DO3A-Lys) cause certain damage on hepatic tissue at high dosage (2.0 mm [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.
Agid:
5996710