Kobayashi Hisataka, Brechbiel Martin W
Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Building 10, Room 1B40, 10 Center Drive, Bethesda, MD 20892-1088, USA.
Adv Drug Deliv Rev. 2005 Dec 14;57(15):2271-86. doi: 10.1016/j.addr.2005.09.016. Epub 2005 Nov 10.
Gadolinium-based MRI contrast agents (CAs) can be effective at a approximately 100-fold lower concentration of Gadolinium ions in comparison to the concentration of Iodine atoms required for CT imaging. Therefore, a number of dendrimer based macromolecular MRI CAs of various sizes and properties prepared employing relatively simple chemistry are readily available that can provide sufficient contrast enhancement for various applications. Molecules up to 20 nm in diameter behave differently in the body depending on their size. Even if these molecules possess similar chemical properties, small changes in size can greatly impact their pharmacokinetics. Changes in molecular size up to 15 nm in diameter altered permeability across the vascular wall, excretion route, and recognition by the reticuloendothelial system. Smaller sized polyamidoamine (PAMAM) dendrimer-based contrast agents, i.e., less than 3 nm in diameter, easily "leak" across the vascular wall resulting in rapid perfusion throughout the body. Contrast agents 3-6 nm in diameter were quickly excreted through the kidney indicating these agents to be potentially suitable as functional renal contrast agents. Contrast agents 7-12 nm in diameter were retained in circulation and were better suited for use as blood pool contrast agents. Hydrophobic variants of CAs formed with polypropylenimine diaminobutane (DAB) dendrimer cores quickly accumulated in the liver and potentially have use as liver contrast agents. Larger hydrophilic agents have suitable characteristics for lymphatic imaging. Finally, contrast agents conjugated with either monoclonal antibodies or with avidin are able to function as tumor-specific contrast agents and might also be employed as either gadolinium neutron capture therapy or in conjunction with radioimmunotherapy.
与CT成像所需的碘原子浓度相比，基于钆的MRI造影剂（CAs）在钆离子浓度约低100倍时仍可有效。因此，利用相对简单的化学方法制备的许多具有各种尺寸和性质的基于树枝状大分子的大分子MRI CAs readily available，可为各种应用提供足够的造影增强。直径达20 nm的分子在体内的行为因其大小而异。即使这些分子具有相似的化学性质，大小的微小变化也会极大地影响其药代动力学。直径达15 nm的分子大小变化会改变其跨血管壁的通透性、排泄途径以及被网状内皮系统识别的情况。基于较小尺寸聚酰胺胺（PAMAM）树枝状大分子的造影剂，即直径小于3 nm的造影剂，很容易“渗漏”穿过血管壁，导致在全身快速灌注。直径为3 - 6 nm的造影剂通过肾脏迅速排泄，表明这些造影剂可能适合作为功能性肾造影剂。直径为7 - 12 nm的造影剂保留在循环中，更适合用作血池造影剂。由聚亚丙基亚胺二氨基丁烷（DAB）树枝状大分子核心形成的CAs的疏水变体迅速在肝脏中积累，可能可用作肝脏造影剂。较大的亲水性造影剂具有适合淋巴成像的特性。最后，与单克隆抗体或抗生物素蛋白偶联的造影剂能够用作肿瘤特异性造影剂，也可能用于钆中子俘获治疗或与放射免疫治疗联合使用。
