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）微球放射栓塞，又称选择性内放射治疗（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。肝脏肿瘤的微血管密度是周围肝实质的3-200倍，进一步提高了治疗对肿瘤的选择性。在这种治疗中，30个直径5米、带有放射性同位素Y-90（一种高能β粒子发射放射性同位素）标记的球体进入肿瘤内的小动脉，摧毁肿瘤，同时基本不损害正常肝组织。为制定治疗计划，将tc -99m巨聚集白蛋白（MAA）注入肝固有动脉，并进行灌注显像。然而，MAA和Y-90微球在尺寸、形状和其他性能上的显著差异使处理计划复杂化，因为不能期望MAA颗粒的分布与Y-90微球相同。因此，开发和使用一种新的可生物降解球体来精确地规划SIRT是可取的。聚乳酸-羟基乙酸（PLGA）、聚酸酐和壳聚糖等可生物降解材料的纳米和微粒在药物传递方面得到了广泛的研究。它们已被证明具有生物相容性和可生物降解性。最近，一种新的合成可生物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。这些聚合物将采用不同的乳液技术，生产大约30个5m大小的可生物降解微球，以匹配处理中使用的Y-90微球的大小和形状。一旦获得，不同的颗粒将在磷酸盐缓冲液中进行体外降解研究，并使用扫描电子显微镜对其形状、大小、尺寸分布、表面粗糙度和孔隙度进行表征。通过肝动脉给药的钇-90 （Y-90）微球放射栓塞，又称选择性内放射治疗（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。还将评估附着在颗粒表面的特定螯合剂（偶联化学品）的使用，以标记产量、放射化学纯度和最终产品的稳定性。项目的最后一步是对颗粒进行体内评价；将在斯普拉格·道利大鼠身上进行评估。这些动物将在不同的时间被安乐死，并收集血液、肺、肝、肾和脾的样本，在伽马井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，并确保达到辐射防护标准。

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. PUBLIC HEALTH RELEVANCE: Colorectal cancer is one of the most common malignancies in industrialized nations, ranking fourth behind lung, breast and prostate cancers. About 140,000 new cases are diagnosed annually in the United States according to the American Cancer Society. A new biodegradable spherical radio-microsphere used for Selective Internal Radiation Therapy (SIRT) planning will decrease the risk of lung and stomach damage, bone marrow suppression, liver and other organs failure that could result from Y-90 SIRT and thus improve the therapeutic effects of the SIRT in patients.