The Biomedical Radiochemistry Laboratory, Department of Applied Mathematics, Research School of Physics and Engineering, Australian National University, Canberra, ACT, Australia,
Animal Services Division, Research School of Biology, Australian National University, Canberra, ACT, Australia.
Int J Nanomedicine. 2019 Jan 31;14:889-900. doi: 10.2147/IJN.S187153. eCollection 2019.
Selective internal radiation therapy (SIRT) is an effective treatment option for liver tumors, using Y-90-loaded polymer microspheres that are delivered via catheterization of the hepatic artery. Since Y-90 is a beta emitter and not conveniently imaged by standard clinical instrumentation, dosimetry is currently evaluated in each patient using a surrogate particle, Technetium-labeled macroaggregated albumin (Tc-MAA). We report a new composite consisting of Tc-labeled nanoparticles attached to the same polymer microspheres as used for SIRT, which can be imaged with standard SPECT.
Carbon nanoparticles with an encapsulated core of Tc were coated with the polycation protamine sulfate to provide electrostatic attachment to anionic polystyrene sulfonate microspheres of different sizes (30, 12, and 8 µm). The in vivo stability of these composites was determined via intravenous injection and entrapment in the capillary network of normal rabbit lungs for up to 3 hours. Furthermore, we evaluated their biodistribution in normal rabbit livers, and livers implanted with VX2 tumors, following intrahepatic artery instillation.
We report distribution tests for three different sizes of radiolabeled microspheres and compare the results with those obtained using Tc-MAA. Lung retention of the radiolabeled microspheres ranged from 72.8% to 92.9%, with the smaller diameter microspheres showing the lowest retention. Liver retention of the microspheres was higher, with retention in normal livers ranging from 99.2% to 99.8%, and in livers with VX2 tumors from 98.2% to 99.2%. The radiolabeled microspheres clearly demonstrated preferential uptake at tumor sites due to the increased arterial perfusion produced by angiogenesis.
We describe a novel use of radiolabeled carbon nanoparticles to generate an imageable microsphere that is stable in vivo under the shear stress conditions of arterial networks. Following intra-arterial instillation in the normal rabbit liver, they distribute in a distinct segmented pattern, with the smaller microspheres extending throughout the organ in finer detail, while still being well retained within the liver. Furthermore, in livers hosting an implanted VX2 tumor, they reveal the increased arterial perfusion of tumor tissue resulting from angiogenesis. These novel composites may have potential as a more representative mimic of the vascular distribution of therapeutic microspheres in patients undergoing SIRT.
选择性内部放射治疗（SIRT）是一种有效的肝脏肿瘤治疗选择，使用载有 Y-90 的聚合物微球，通过肝动脉导管插入术输送。由于 Y-90 是一种 β 发射器，并且不能通过标准临床仪器方便地成像，因此目前在每个患者中使用替代粒子，锝标记的聚合白蛋白（Tc-MAA）来评估剂量。我们报告了一种由附着在用于 SIRT 的相同聚合物微球上的 Tc 标记纳米颗粒组成的新型复合材料，该复合材料可以使用标准 SPECT 进行成像。
用 Tc 封装的核心包裹碳纳米颗粒，并用聚阳离子鱼精蛋白硫酸盐进行涂层，以提供与不同大小（30、12 和 8 µm）的阴离子聚苯乙烯磺酸盐微球的静电附着。通过静脉内注射和长达 3 小时的毛细血管网络内捕获，确定这些复合材料的体内稳定性。此外，我们评估了它们在正常兔肝脏中的生物分布，并在肝内动脉滴注后评估了它们在植入 VX2 肿瘤的肝脏中的生物分布。
我们报告了三种不同大小的放射性标记微球的分布测试，并将结果与使用 Tc-MAA 获得的结果进行了比较。放射性标记微球在肺部的滞留率范围为 72.8%至 92.9%，直径较小的微球的滞留率最低。微球在肝脏中的滞留率较高，在正常肝脏中的滞留率范围为 99.2%至 99.8%，在植入 VX2 肿瘤的肝脏中的滞留率为 98.2%至 99.2%。由于血管生成导致的动脉灌注增加，放射性标记的微球明显优先在肿瘤部位摄取。
我们描述了一种新型的放射性标记碳纳米颗粒的用途，用于生成可成像的微球，该微球在动脉网络的剪切应力条件下在体内稳定。在正常兔肝脏内动脉内滴注后，它们以明显的分段模式分布，较小的微球更详细地延伸到整个器官，而仍在肝脏中很好地保留。此外，在植入 VX2 肿瘤的肝脏中，它们揭示了血管生成导致的肿瘤组织的动脉灌注增加。这些新型复合材料可能具有作为接受 SIRT 的患者中治疗性微球血管分布更具代表性的模拟物的潜力。
