High Relaxivity Magnetic Resonance Imaging Contrast Agents Part 1 Impact of Single Donor Atom Substitution on Relaxivity of Serum Albumin-Bound Gadolinium Complexes
High Relaxivity Magnetic Resonance Imaging Contrast Agents Part 1 Impact of Single Donor Atom Substitution on Relaxivity of Serum Albumin-Bound Gadolinium Complexes
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DOI：
10.1097/rli.0b013e3181ee5a9e
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发表时间：
2010-10-01
影响因子：
6.7
通讯作者：
Caravan, Peter
中科院分区：
文献类型：
--
作者：
Dumas, Stephane;Jacques, Vincent;Caravan, Peter
基本原理和目标：在造影剂中与钆结合的供体原子影响内球水交换和电子弛豫，这两者都决定了观察到的弛豫。当造影剂与蛋白质结合时，这些分子参数对弛豫率的影响最大。我们试图确定一个最佳的供体原子集，以产生高relaxivitycompounds.Methods：共38钆-1，4，7，10-tetraazacyclo-dodecane-N，N '，N“”，N“”-四乙酰基衍生物的制备和弛豫率测定在存在和不存在的人血清白蛋白作为温度和磁场的函数。每种化合物都有一个共同的白蛋白结合基团，不同之处仅在于大环氮上不同供体基团的取代。氧-17同位素弛豫法在7.05 T进行估计水exchange rates.Results：改变一个单一的供体原子导致水交换率的变化范围跨越3个数量级。供体基团增加水交换速率的顺序为膦酸酯>苯酚酯> α-取代乙酸酯>乙酸酯>异羟肟酸酯>磺酰胺>酰胺>吡啶基>咪唑。在0.47和1.4 T，37 ℃下，弛豫时间分别为12.3至55.6 mM（-1）s（-1）和8.3至32.6 mM（-1）s（-1）。当供体基团是α-取代的乙酸酯时，观察到最佳弛豫率。电子弛豫是最慢的乙酸酯衍生物，以及。结论：水交换动力学和弛豫可以通过选择施主原子可预测地调整。
Rationale and Objectives: The donor atoms that bind to gadolinium in contrast agents influence inner-sphere water exchange and electronic relaxation, both of which determine observed relaxivity. The effect of these molecular parameters on relaxivity is greatest when the contrast agent is protein bound. We sought to determine an optimal donor atom set to yield high relaxivity compounds.Methods: A total of 38 gadolinium-1,4,7,10-tetraazacyclo-dodecane-N, N',N '', N'''-tetraacetato derivatives were prepared and relaxivity was determined in the presence and absence of human serum albumin as a function of temperature and magnetic field. Each compound had a common albumin-binding group and differed only by substitution of different donor groups at one of the macrocycle nitrogens. Oxygen-17 isotope relaxometry at 7.05 T was performed to estimate water exchange rates.Results: Changing a single donor atom resulted in changes in water exchange rates ranging across 3 orders of magnitude. Donor groups increased water exchange rate in the order: phosphonate > phenolate > alpha-substituted acetate > acetate > hydroxamate > sulfonamide > amide > pyridyl > imidazole. Relaxivites at 0.47 and 1.4 T, 37 degrees C, ranged from 12.3 to 55.6 mM(-1)s(-1) and from 8.3 to 32.6 mM(-1)s(-1) respectively. Optimal relaxivities were observed when the donor group was an alpha-substituted acetate. Electronic relaxation was slowest for the acetate derivatives as well.Conclusions: Water exchange dynamics and relaxivity can be predictably tuned by choice of donor atoms.