Imaging for Y90 Microscphere SIRT Planning

描述（由申请人提供）：通过肝动脉给药的钇-90（Y-90）微球放射性栓塞，称为选择性内部放射治疗（SIRT），是原发性和转移性肝癌患者的一种治疗方法，因为肝脏肿瘤的主要血液供应来自肝动脉，而正常肝脏的大部分血液供应来自门静脉。肝肿瘤的微血管密度是周围肝实质的3-200倍，进一步提高了对肿瘤治疗的选择性。在这种治疗中，30个直径为5米的球用放射性同位素Y-90（一种高能β粒子发射放射性同位素）标记，卡在肿瘤内的小动脉中，摧毁肿瘤，同时使正常的肝组织基本上不受伤害。对于治疗计划，将Tc-99 m-大聚集白蛋白（MAA）输注到肝固有动脉中，并进行灌注造影术。然而，MAA和Y-90微球在尺寸、形状和其他性质上的显著差异使治疗计划复杂化，因为不能期望MAA颗粒与Y-90微球相同地分布。因此，需要开发和使用新的可生物降解的球体用于精确的SIRT规划。聚乳酸-羟基乙酸共聚物（PLGA）、聚酸酐、壳聚糖等可生物降解材料的纳米和微米粒已被广泛研究用于药物递送。它们已被证明是生物相容性和生物可降解的。最近，一种新的合成生物可降解弹性体聚（甘油十二烷二酸酯）（PGD）已被开发用于医疗器械和组织工程支架。将使用这些聚合物，采用不同的乳液技术，以产生约30 5 μ m大小的生物可降解微球，以匹配治疗中使用的Y-90微球的大小和形状。一旦获得，将在磷酸盐缓冲液中对不同颗粒进行体外降解研究，并使用扫描电子显微镜表征形状、尺寸、尺寸分布、表面粗糙度和孔隙率。钇-90（Y-90）微球放射性栓塞，被称为选择性内部放射治疗（SIRT），通过肝动脉给药，是原发性和转移性肝癌患者的治疗方法，因为肝脏肿瘤的主要血液供应来自肝动脉，而正常肝脏的大部分血液供应来自门静脉。还将评价使用附着于颗粒表面的特定螯合剂（偶联化学品）的标记产率、放射化学纯度和最终产品的稳定性。该项目的最后一步是颗粒的体内评价;将在Sprague道利大鼠中进行评价。将在不同时间对动物实施安乐死，并采集血液、肺、肝、肾和脾样本，用于在伽马孔计数器中测量放射性含量。将进行数值剂量学计算，以评估辐射场和剂量分布，并确保符合辐射防护标准。

DESCRIPTION (provided by applicant): Yttrium-90 (Y-90) microsphere radioembolization, known as Selective Internal Radiation Therapy (SIRT), via hepatic arterial administration is a treatment for patients with primary and metastatic liver cancer because the primary blood supply to liver tumors is from the hepatic artery while the majority of the blood supply to the normal liver is from the portal vein. The micro-vascular density of liver tumors is 3-200 times greater than the surrounding liver parenchyma further improving the selectivity of the therapy to the tumor. In this treatment, 30 5m diameter spheres labeled with the radioactive isotope Y-90 (a high-energy beta particle-emitting radioisotope) become lodged in the arterioles within the tumor and destroy the tumor while leaving the normal liver tissue mostly unharmed. For treatment planning Tc-99m-macro aggregated albumin (MAA) is infused into the proper hepatic artery and a perfusion scintigraphy is performed. However, the significant difference in size, shape, and other properties of the MAA and the Y-90 microspheres complicates the treatment planning because the MAA particles cannot be expected to distribute the same as the Y-90 microspheres. Thus it is desirable to develop and use a new biodegradable sphere for accurate SIRT planning. Nano and microparticles of biodegradable materials like Poly(lactic-co-glycolic acid) (PLGA), Polyanhydrides, and Chitosan, have been investigated widely for drug delivery. They have been shown to be both biocompatible and biodegradable. More recently, a new synthetic biodegradable elastomer Poly(glycerol Dodecanedioate) (PGD) has been developed for medical devices and tissue engineering scaffolds. These polymers will be used, employing different emulsion techniques, to produce approximately 30 5m size biodegradable microspheres to match the size and shape of the Y-90 microspheres used in the treatment. Once obtained, the different particles will be submitted to in vitro degradation studies in phosphate buffer and characterized with respect to shape, size, size distribution, surface roughness, and porosity using scanning electron microscope. Yttrium-90 (Y-90) microsphere radioembolization, known as Selective Internal Radiation Therapy (SIRT), via hepatic arterial administration is a treatment for patients with primary and metastatic liver cancer because the primary blood supply to liver tumors is from the hepatic artery while the majority of the blood supply to the normal liver is from the portal vein. The use of a specific chelator (coupling chemical) attached to the surface of the particles will also be evaluated for labeling yields, radiochemical purity and stability of the final product. The final step of the project is the in vivo evaluation of the particles; which will be evaluated in Sprague Dawley rats. The animals will be euthanized at different times and the samples of blood, lung, liver, kidney, and spleen will be collected for measuring of radioactive content in a gamma well counter. Numerical dosimetry calculations will be done to evaluate the radiation field and dose distributions and assure radioprotection standards are met.