Synthesis and Characterization of HE-24.8: A Polymeric Contrast Agent for Magnetic Resonance Angiography

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• 作者：Fabian Kiessling ; Melanie Heilmann ; Twan Lammers ; Karel Ulbrich ; Vladimir Subr ; Peter Peschke ; Bjoern Waengler ; Walter Mier ; Hans-Herrmann Schrenk ; Michael Bock ; Lothar Schad ; and Wolfhard Semmler
• 刊名：Bioconjugate Chemistry
• 出版年：2006
• 出版时间：January 2006
• 年：2006
• 卷：17
• 期：1
• 页码：42 - 51
• 全文大小：640K
• 年卷期：v.17,no.1(January 2006)
• ISSN：1520-4812

文摘

The physical and biological properties of a water-soluble polymeric contrast agent based on a complex of N-(2-hydroxypropyl)methacrylamide copolymer with gadolinium (HE-24.8) were investigated, and its potential forexperimental magnetic resonance (MR) angiography was assessed. Relaxivities of Gd-DTPA-BMA, Gd-DTPA-HSA (human serum albumin), and HE-24.8 were determined at 1.5 T. Thermic stability and biocompatibility ofHE-24.8 were assessed in vitro and by analyzing kinetics and organ distribution in rats for up to 2 weeks. Forcomparison, HE-24.8- and Gd-DTPA-HSA-enhanced micro-MR angiographies of brain, chest, and subcutaneoustumors in rats were performed. T₁ relaxivity of HE-24.8 (21.3 ± 1.1 mM^-1 s^-1) was 5-fold higher than that ofGd-DTPA-BMA (4.1 ± 0.1 mM^-1 s^-1) and twice as high as that of Gd-DTPA-HSA (12.4 ± 0.2 mM^-1 s^-1).Varying the molecular weight of the polymer (15-46 kDa) did not significantly change the T₁ relaxivity. In rats,20 and 10% of the injected dose of HE-24.8 was detected at 24 and 168 h postinjection, respectively. Upon arelatively rapid initial renal clearance, no specific retention in any organ was noted, with some exception for thereticulo-endothelial system. No measurable release of gadolinium from the polymer-Gd complex or cell toxicitywas observed during its incubation in aqueous environment. Excellent display of rat and tumor vascularizationwas achieved with Gd-DTPA-HSA and HE-24.8; however, contrast of vessels was higher in HE-24.8-enhancedscans. HE-24.8 is considered a macromolecular contrast agent highly suited for experimental MR studies.