Leung Kam
National for Biotechnology Information, NLM, NIH, Bethesda, MD
Magnetic resonance imaging (MRI) maps information about tissues spatially and functionally (1). Protons (hydrogen nuclei) are widely used in imaging because of their abundance in water molecules. Water comprises 80% of most soft tissue. The contrast of proton MRI depends primarily on the density of the nucleus (proton spins), the relaxation times of the nuclear magnetization (T1, longitudinal, and T2, transverse), the magnetic environment of the tissues, and the blood flow to the tissues. However, insufficient contrast between normal and diseased tissues requires the development of contrast agents. Most contrast agents affect the T1 and T2 relaxation times of the surrounding nuclei, mainly the protons of water. T2* is the spin–spin relaxation time composed of variations from molecular interactions and intrinsic magnetic heterogeneities of tissues in the magnetic field. Cross-linked iron oxide nanoparticles and other iron oxide formulations affect T2 primarily and lead to decreased signals. On the other hand, paramagnetic T1 agents, such as gadolinium (Gd) and manganese (Mn), accelerate T1 relaxation and lead to brighter contrast images (2). Gadolinium (Gd), a lanthanide metal ion with seven unpaired electrons, has been shown to be very effective in enhancing proton relaxation because of its high magnetic moment and water coordination (3, 4). Gd-Labeled diethylenetriamine pentaacetic acid (Gd-DTPA) was the first intravenous MRI contrast agent used clinically, and a number of similar Gd chelates have been developed in an effort to further improve clinical use. However, these low molecular weight Gd chelates have short blood and tissue retention times, which limit their use as imaging agents in the vasculature and cancer. Furthermore, these low molecular weight MRI contrast agents exhibit low relaxivity value (4 mMs per Gd), high toxicity (nephrogenic systemic fibrosis in patients with renal dysfunction), and a lack of tissue specificity (5). Li et al. (6) have developed polyhedral boranes as a scaffold for the targeted high payload delivery of drugs and imaging agents. A functionalizable monodisperse molecular borane scaffold, [closoB(OH)], conjugated with twelve radial ethylene glycol (PEG) arms with attachments of Gd-labeled diethylenetriamine tetraacetic acid (Gd-DTTA) (CA-9). Goswami et al. (7) evaluated CA-9 for use as a high-performance MRI contrast agent in nude mice bearing human PC-3 prostate tumors.
磁共振成像（MRI）能在空间和功能上绘制组织信息（1）。质子（氢原子核）因其在水分子中含量丰富而被广泛用于成像。水占大多数软组织的约80%。质子MRI的对比度主要取决于原子核的密度（质子自旋）、核磁化的弛豫时间（纵向的T1和横向的T2）、组织的磁环境以及组织的血流情况。然而，正常组织与病变组织之间的对比度不足，这就需要研发造影剂。大多数造影剂会影响周围原子核的T1和T2弛豫时间，主要是水分子中的质子。T2*是由分子相互作用以及磁场中组织的固有磁不均匀性引起的自旋-自旋弛豫时间。交联氧化铁纳米颗粒和其他氧化铁制剂主要影响T2并导致信号减弱。另一方面，顺磁性T1造影剂，如钆（Gd）和锰（Mn），会加速T1弛豫并产生对比度更高的明亮图像（2）。钆（Gd）是一种具有七个未成对电子的镧系金属离子，由于其高磁矩和与水的配位作用，已被证明在增强质子弛豫方面非常有效（3,4）。钆标记的二乙烯三胺五乙酸（Gd-DTPA）是临床上首个使用的静脉注射MRI造影剂，为进一步改善临床应用，人们还研发了许多类似的钆螯合物。然而，这些低分子量的钆螯合物在血液和组织中的保留时间较短，这限制了它们在血管系统和癌症成像中的应用。此外，这些低分子量的MRI造影剂弛豫率值较低（每钆约4 mM s⁻¹）、毒性较高（肾功能不全患者会发生肾源性系统性纤维化）且缺乏组织特异性（5）。李等人（6）研发了多面体硼烷作为药物和成像剂靶向高负载递送的支架。一种可功能化的单分散分子硼烷支架[closoB(OH)₃]，与十二个带有钆标记的二乙烯三胺四乙酸（Gd-DTTA）（CA-9）附着的径向乙二醇（PEG）臂共轭。戈斯瓦米等人（7）评估了CA-9在携带人PC-3前列腺肿瘤的裸鼠中作为高性能MRI造影剂的用途。
