Department of Radiology, University Medical Center Utrecht, Utrecht, The Netherlands.
Department of Radiology, University Medical Center Utrecht, Utrecht, The Netherlands.
Int J Pharm. 2015 Mar 30;482(1-2):47-53. doi: 10.1016/j.ijpharm.2014.11.010. Epub 2014 Nov 6.
Embolotherapy is a minimally invasive transcatheter technique aiming at reduction or complete obstruction of the blood flow by infusion of micro-sized particles in order to induce tumor regression. A major drawback of the current commercially available and clinically used microspheres is that they cannot be detected in vivo with medical imaging techniques, impeding intra- and post-procedural feedback. It can be expected that real-time monitoring of microsphere infusion and post-procedural imaging will result in better predictability and higher efficacy of the treatment. In this study, a novel microsphere formulation has been developed that can be visualized with fluoroscopy, X-ray computed tomography (CT) and magnetic resonance imaging (MRI). The microspheres were prepared with the JetCutter technique and consist of alginate (matrix-forming polymer), holmium (cross-linking and MRI contrast agent), lipiodol (radiopaque contrast agent) and Pluronic F-68 (surfactant). The mean size (±SEM) of the hydrated holmium-lipiodol-alginate microspheres (Ho-lip-ams) was 570±12 μm with a holmium content of 0.38±0.01% (w/w). Stability studies showed that the microspheres remained intact during incubation for two weeks in fetal calf serum (FCS) at 37 °C. The inclusion of lipiodol in the microspheres rendered excellent visualization capabilities for fluoroscopy and CT, whereas the holmium ions, which keep the alginate network together, also allow MR imaging. In this study it was shown that single sphere detection was possible by fluoroscopy, CT and MRI. The Ho-lip-ams were visualized in real-time, during infusion in a porcine kidney using fluoroscopy, and post-procedural, the deposition of the microspheres was examined with fluoroscopy, (cone beam rotational) CT and MRI. The different imaging modalities showed similar deposition patterns of the microspheres within the organ. The combination of intra-procedural visualization, multimodality imaging for patient follow-up and the possibility of quantification offers a new and promising method for more safe, efficient and successful embolization treatment.
栓塞疗法是一种微创经导管技术，通过输注微球来减少或完全阻断血流，以诱导肿瘤消退。目前市售和临床应用的微球的一个主要缺点是它们不能通过医学成像技术在体内检测到，这阻碍了术中及术后的反馈。可以预期，实时监测微球输注和术后成像将提高治疗的可预测性和疗效。在这项研究中，开发了一种新的微球制剂，可以通过透视、X 射线计算机断层扫描（CT）和磁共振成像（MRI）进行可视化。这些微球是通过 JetCutter 技术制备的，由海藻酸钠（基质形成聚合物）、钬（交联和 MRI 造影剂）、碘化油（不透射线造影剂）和 Pluronic F-68（表面活性剂）组成。水合钬-碘化油-海藻酸钠微球（Ho-lip-ams）的平均粒径（±SEM）为 570±12μm，钬含量为 0.38±0.01%（w/w）。稳定性研究表明，微球在 37°C 的胎牛血清（FCS）中孵育两周仍保持完整。碘化油的加入使微球在透视和 CT 下具有极好的可视化能力，而保持海藻酸钠网络在一起的钬离子也允许磁共振成像。在这项研究中，证明了透视、CT 和 MRI 可以检测单个微球。在透视下，钬-碘化油-海藻酸钠微球在猪肾内输注过程中实时可视化，术后，用透视、（锥形束旋转）CT 和 MRI 检查微球的沉积情况。不同的成像方式显示了微球在器官内的沉积模式相似。术中可视化、多模态成像用于患者随访以及量化的可能性为更安全、更有效和更成功的栓塞治疗提供了一种新的、有前途的方法。
