Application of High-spin Species Designed by the Studies on Molecule-based on Magnet to MRI ImagingAgents

用于MRI成像剂的分子需要在水中的高溶解度和水质子的高弛豫率r_1和r_2。影响水质子弛豫时间的因素之一是磁共振成像剂分子的转动相关时间（τ R），弛豫率随τR值的增大而增大。由于τ R值受分子大小的影响; τR与r ^3成正比，其中r是球形分子的半径，因此分子量大的分子预计会产生高弛豫率。基于这个想法，我们进行了两种方法，DNA和树枝状聚合物系统。在DNA体系中，制备了带有稳定自由基的DNA单体、其寡聚体（15聚体）和其与互补DNA寡聚体的双链体，并用脉冲核磁共振谱研究了它们的弛豫特性。所得r_1和r_2值随分子量的增加而增加。单体、寡聚体和双链体衍生物的r_1值分别为0.25、0.44和0.57 sec·<-1>mM·cm-2<-1>。在水溶性树枝状大分子体系中，通过离子交换反应，可以将十六个稳定的自由基单元引入到带有羧酸基团的胺树枝状大分子的第三代。获得r_1= 2.28秒/<-1>mM/<-1>分子的值。该系统通过使用超支化聚合物（HBP）进行改进，并且在现阶段获得了高于作为钆络合物并用于临床领域的Magenvist的值。

The molecule for MRI imaging agent requires the high solubility in water and the high relaxivities, r_1 and r_2, of the water proton. One of the factors affecting to the relaxation time of the water proton is the rotational correlation time (τ_R) of the molecule for MRI imaging agent and the relaxivities increase with increasing the τR value. Because the τ_R value is affected by the size of the molecule; τR is proportional to r^3, where r is a radius of the molecule spherical in shape, the molecule with large molecular weight is expected to give high relaxivities. Based on this idea, we performed two approaches, DNA and dendrimer systems. In DNA system, the DNA monomer carrying a stable radical, its oligomer (15mer), and its duplex with a complimentary DNA oligomer were prepared and their relaxivities were investigated by a pulse NMR spectrometry. Obtained values of r_1 and r_2 increased with increasing the molecular weight, as expected. The values of r_1 for a monomer, an oligomer, and a duplex derivatives are 0.25, 0.44, and 0.57 sec^<-1>mM^<-1>, respectively. In water-soluble dendrimer system, sixteen stable radical units could be introduced to the third generation in the amine dendrimer carrying the carboxylic acid moieties by an ion exchange reaction. The value of r_1= 2.28 sec^<-1>mM^<-1> per molecule was obtained. This system is improved by using a hyper-branched polymer (HBP) and the value higher than the one for the Magnevist which is a gadolinium complex and is used in clinical field, is obtained at present stage.