Bifunctional chelates optimized for molecular MRI.
Bifunctional chelates optimized for molecular MRI.
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针对分子 MRI 优化的双功能螯合物。
DOI：
10.1021/ic500085g
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发表时间：
2014-07-07
影响因子：
4.6
通讯作者：
Rheingold AL
中科院分区：
文献类型：
--
作者：
Wiener EC;Abadjian MC;Sengar R;Vander Elst L;Van Niekerk C;Grotjahn DB;Leung PY;Schulte C;Moore CE;Rheingold AL
在磁共振成像(MRI)中，对外源染料或造影剂的重要要求包括在要成像的目标处有效地聚集顺磁或超顺磁性离子。本文报道了几种新的对映体双功能衍生物(α10-tetramethyl-1，4，7，10-tetraazacyclododecane-1，4，7，10-tetraacetic 1R，α4R，α7R，α10R)-α1，α4，α7，DOTMA(以及它们的DOTA类似物作为对照)的简单合成和表征，它们可以通过点击或多肽偶联化学的方式共价连接到造影剂递送系统上。这些衍生物的Gd络合物可以附着在传递系统上，同时保持最佳的水停留时间，以提高分子成像灵敏度。与亲和素相关的Eu(III)和Gd(III)螯合物的长链生物素(LC-生物素)衍生物被用于展示更高的效率。变温弛豫法、17O核磁共振和核磁共振弥散(NMRD)谱用于测定水的滞留时间和旋转关联时间对受限和非受限体系的影响。Gd(III)-DOTMA衍生物比Gd(III)-DOTA衍生物具有更短的水停留时间。与受限的Gd(III)-DOTA衍生物相比，旋转受限的Gd(III)-DOTMA衍生物在37°C具有高40%的∼弛豫度，这可以提高其作为核磁共振成像剂的灵敏度，同时减少靶向剂的剂量。用于Gd基造影剂的DOTMA对映体双功能衍生物的多克制备将使通过点击或酰胺键化学与靶向系统偶联成为可能。Gd(III)-DOTMA衍生物比Gd(III)-DOTA衍生物具有更短的水停留时间。用生物素−亲和素络合作用比较约束体系，Gd(III)-DOTMA衍生物在37℃时的弛豫度比DOTA类似物高40%，这可以提高其作为有效磁共振成像剂的灵敏度。
Important requirements for exogenous dyes or contrast agents in magnetic resonance imaging (MRI) include an effective concentration of paramagnetic or superparamagnetic ions at the target to be imaged. We report the concise synthesis and characterization of several new enantiopure bifunctional derivatives of (α1R,α4R,α7R,α10R)-α1,α4,α7,α10-tetramethyl-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTMA) (and their 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) analogues as controls) that can be covalently attached to a contrast agent delivery system using either click or peptide coupling chemistry. Gd complexes of these derivatives can be attached to delivery systems while maintaining optimal water residence time for increased molecular imaging sensitivity. Long chain biotin (LC-biotin) derivatives of the Eu(III) and Gd(III) chelates associated with avidin are used to demonstrate higher efficiencies. Variable-temperature relaxometry, 17O NMR, and nuclear magnetic resonance dispersion (NMRD) spectroscopy used on the complexes and biotin–avidin adducts measure the influence of water residence time and rotational correlation time on constrained and unconstrained systems. The Gd(III)-DOTMA derivative has a shorter water residence time than the Gd(III)-DOTA derivative. Compared to the constrained Gd(III)-DOTA derivatives, the rotationally constrained Gd(III)-DOTMA derivative has ∼40% higher relaxivity at 37 °C, which could increase its sensitivity as an MRI agent as well as reduce the dose of the targeting agent. Multigram preparation of enantiopure bifunctional derivatives of DOTMA for Gd-based contrast agents will enable coupling to targeting systems via click or amide-bond chemistry. The Gd(III)-DOTMA derivative has a shorter water residence time than the Gd(III)-DOTA derivative. Using biotin−avidin complexation to compare constrained systems, the Gd(III)-DOTMA derivative has ∼40% higher relaxivity at 37 °C compared to the DOTA analogue, which could increase its sensitivity as an efficient MRI agent.
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影响因子：
6.7
作者：
Dumas, Stephane;Jacques, Vincent;Caravan, Peter
通讯作者：
Caravan, Peter
影响因子：
4.6
作者：
Avedano, Stefano;Botta, Mauro;Woods, Mark
通讯作者：
Woods, Mark
影响因子：
4.6
作者：
AIME, S;BOTTA, M;VIRTUANI, M
通讯作者：
VIRTUANI, M
影响因子：
2.8
作者：
Abramson, Sarah;Berkovich-Berger, Dvora;Fuchs, Benzion
通讯作者：
Fuchs, Benzion
影响因子：
4.6
作者：
BRITTAIN, HG;DESREUX, JF
通讯作者：
DESREUX, JF