Maximizing T2-exchange in Dy(3+)DOTA-(amide)X chelates: fine-tuning the water molecule exchange rate for enhanced T2 contrast in MRI.

Maximizing T2-exchange in Dy(3+)DOTA-(amide)X chelates: fine-tuning the water molecule exchange rate for enhanced T2 contrast in MRI.
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DOI:
10.1002/mrm.25091
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发表时间:
2014-03
影响因子:
3.3
通讯作者:
Sherry, A. Dean
Sherry, A. Dean
中科院分区:
医学3区
文献类型:
--
作者:
Soesbe, Todd C.;Ratnakar, S. James;Milne, Mark;Zhang, Shanrong;Do, Quyen N.;Kovacs, Zoltan;Sherry, A. Dean

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微调一系列DyDOTA-(酰胺)X螯合物中的水分子交换速率以使T2交换谱线加宽的效果最大化并改善T2对比度。制备具有可变数目的甘氨酸侧臂的四种DyDOTA-(酰胺)X螯合物,并表征为T2交换剂。非交换DyTETA螯合物也用于测量仅由于T2* 导致的本体水T2减少。在9.4 T(400 MHz)下,通过拟合总T2−1与浓度的关系图,在体外测量了每种螯合物在22、37和52 °C下的总横向弛豫率(r2 tot)。通过拟合17 O线宽与在9.4 T(54.3 MHz)下获得的温度数据来测量每个复合物的水分子交换速率。由于水分子交换而测得的横向弛豫率(r2 ex)和束缚水寿命(τM)与Swift-Connick理论非常一致,DyDOTA-(gly)3在37 °C下给出最大的r2 ex = 11.8 s−1 mM−1。通过在37 °C下微调水分子交换速率,与先前研究的基于Dy 3+的螯合物相比,横向弛豫率增加了2至30倍。最佳螯合物的聚合或树枝状聚合可以产生用于改进的分子成像应用的高灵敏度的分子大小的T2造影剂。
The water molecule exchange rates in a series of DyDOTA-(amide)X chelates were fine-tuned to maximize the effects of T2-exchange line broadening and improve T2 contrast. Four DyDOTA-(amide)X chelates having a variable number of glycinate side-arms were prepared and characterized as T2-exchange agents. The non-exchanging DyTETA chelate was also used to measure the bulk water T2 reduction due solely to T2*. The total transverse relaxivity (r2tot) at 22, 37, and 52 °C for each chelate was measured in vitro at 9.4 T (400 MHz) by fitting plots of total T2−1 versus concentration. The water molecule exchange rates for each complex were measured by fitting 17O line-width versus temperature data taken at 9.4 T (54.3 MHz). The measured transverse relaxivities due to water molecule exchange (r2ex) and bound water lifetimes (τM) were in excellent agreement with Swift-Connick theory, with DyDOTA-(gly)3 giving the largest r2ex = 11.8 s−1 mM−1 at 37 °C. By fine-tuning the water molecule exchange rate at 37 °C, the transverse relaxivity has been increased by 2 to 30 times compared to previously studied Dy3+-based chelates. Polymerization or dendrimerization of the optimal chelate could yield a highly sensitive, molecule-sized T2 contrast agent for improved molecular imaging applications.
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