Imaging for Y90 Microscphere SIRT Planning

描述(申请人提供)：Y-90(Y-90)微球放射栓塞术，称为选择性内放射治疗(SIRT)，通过肝动脉给药是一种治疗原发性和转移性肝癌患者的方法，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。肝肿瘤的微血管密度是周围肝实质的3-200倍，进一步提高了治疗对肿瘤的选择性。在这种治疗中，30个直径5米的标记有放射性同位素Y-90(一种发射高能β粒子的放射性同位素)的球体滞留在肿瘤内的小动脉中，摧毁肿瘤，而正常肝组织几乎没有受到损害。为了制定治疗计划，将~(99m)Tc-大分子聚集白蛋白(MAA)注入肝固有动脉，并进行灌注核素扫描。然而，MAA和Y-90微球在大小、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微球分布相同。因此，开发和使用一种新的生物可降解球体以进行准确的SIRT规划是可取的。聚乳酸-乙醇酸共聚物(PLGA)、聚酸酐和壳聚糖等生物可降解材料的纳米和微米颗粒在药物输送方面已被广泛研究。它们已经被证明是生物相容性和可生物降解性的。最近，一种用于医疗器械和组织工程支架的新型合成可生物降解弹性体聚(十二碳二酸甘油)(PGD)被开发出来。这些聚合物将使用不同的乳化技术，以生产大约30 5米大小的可生物降解微球，以匹配治疗中使用的Y-90微球的大小和形状。一旦获得，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、表面粗糙度和孔隙率进行表征。Y-90(Y-90)微球放射栓塞术，即选择性内放射治疗(SIRT)，经肝动脉给药是治疗原发性和转移性肝癌的一种方法，因为肝肿瘤的主要供血来自肝动脉，而正常肝脏的大部分供血来自门静脉。还将评估使用附着在颗粒表面的特定螯合剂(偶联剂)来标记最终产品的产率、放射化学纯度和稳定性。该项目的最后一步是对这些颗粒进行体内评估；这将在SpragueDawley大鼠身上进行评估。动物将在不同的时间被安乐死，血液、肺、肝、肾和脾的样本将被收集，用于在伽马井计数器中测量放射性含量。将进行数值剂量计算，以评估辐射场和剂量分布，并确保满足辐射防护标准。 公共卫生相关性：结直肠癌是工业化国家最常见的恶性肿瘤之一，仅次于肺癌、乳腺癌和前列腺癌，排名第四。根据美国癌症协会的数据，美国每年约有14万新确诊病例。一种新型的可生物降解的球形放射微球用于选择性内放射治疗(SIRT)计划，将降低Y-90 SIRT可能导致的肺和胃损伤、骨髓抑制、肝脏和其他器官衰竭的风险，从而提高SIRT的疗效。

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.