Synthesis and Evaluation of a High Relaxivity Manganese(II)-Based MRI Contrast Agent
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- 作者：Jeffrey S. Troughton ; Matthew T. Greenfield ; Jaclyn M. Greenwood ; Sté ; phane Dumas ; Andrea J. Wiethoff ; Jufeng Wang ; Marga Spiller ; Thomas J. McMurry ; and Peter Caravan
- 刊名：Inorganic Chemistry
- 出版年：2004
- 出版时间：October 4, 2004
- 年：2004
- 卷：43
- 期：20
- 页码：6313 - 6323
- 全文大小：177K
- 年卷期：v.43,no.20(October 4, 2004)
- ISSN：1520-510X
文摘
The manganese(II) ion has many favorable properties that lead to its potential use as an MRI contrast agent: highspin number, long electronic relaxation time, labile water exchange. The present work describes the design, synthesis,and evaluation of a novel Mn(II) complex (MnL1) based on EDTA and also contains a moiety that noncovalentlybinds the complex to serum albumin, the same moiety used in the gadolinium based contrast agent MS-325.Ultrafiltration albumin binding measurements (0.1 mM, pH 7.4, 37 
C) indicated that the complex binds well toplasma proteins (rabbit: 96 ± 2% bound, human: 93 ± 2% bound), and most likely to serum albumin (rabbit: 89± 2% bound, human 98 ± 2% bound). Observed relaxivities (± 5%) of the complex were measured (20 MHz, 37C, 0.1 mM, pH 7.4) in HEPES buffer (r1 = 5.8 mM-1 s-1), rabbit plasma (r1 = 51 mM-1 s-1), human plasma (r1= 46 mM-1 s-1), 4.5% rabbit serum albumin (r1 = 47 mM-1 s-1), and 4.5% human serum albumin (r1 = 48 mM-1s-1). The water exchange rate was near optimal for an MRI contrast agent (k298 = 2.3 ± 0.9 × 108 s-1). Variabletemperature NMRD profiles indicated that the high relaxivity was due to slow tumbling of the albumin-bound complexand fast exchange of the inner sphere water. The concept of a high relaxivity Mn(II)-based contrast agent wasvalidated by imaging at 1.5T. In a rabbit model of carotid artery injury, MnL1 clearly delineated both arteries andveins while also distinguishing between healthy tissue and regions of vessel damage.
C) indicated that the complex binds well toplasma proteins (rabbit: 96 ± 2% bound, human: 93 ± 2% bound), and most likely to serum albumin (rabbit: 89± 2% bound, human 98 ± 2% bound). Observed relaxivities (± 5%) of the complex were measured (20 MHz, 37C, 0.1 mM, pH 7.4) in HEPES buffer (r1 = 5.8 mM-1 s-1), rabbit plasma (r1 = 51 mM-1 s-1), human plasma (r1= 46 mM-1 s-1), 4.5% rabbit serum albumin (r1 = 47 mM-1 s-1), and 4.5% human serum albumin (r1 = 48 mM-1s-1). The water exchange rate was near optimal for an MRI contrast agent (k298 = 2.3 ± 0.9 × 108 s-1). Variabletemperature NMRD profiles indicated that the high relaxivity was due to slow tumbling of the albumin-bound complexand fast exchange of the inner sphere water. The concept of a high relaxivity Mn(II)-based contrast agent wasvalidated by imaging at 1.5T. In a rabbit model of carotid artery injury, MnL1 clearly delineated both arteries andveins while also distinguishing between healthy tissue and regions of vessel damage.