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Imaging for Y90 Microscphere SIRT Planning

Y90 微球 SIRT 规划的成像

基本信息

批准号：
8269824
负责人：
Anthony J McGoron
金额：
$ 18.54万
依托单位：
FLORIDA INTERNATIONAL UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-06-01 至 2014-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8269824
关键词：
90Y Albumins American Cancer Society Anatomy Angiography Animals Beta Particle Bile duct carcinoma Biocompatible Biodegradable microsphere Biodegradation Biodistribution Blood Vessels Blood specimen Bone Marrow Suppression Caliber Chelating Agents Chemicals Chemistry Chitosan Clinical Code Colorectal Colorectal Cancer Computer software Coupling Deposition Detection Developed Countries Diagnosis Discipline of Nuclear Medicine Dose Drug Delivery Systems Drug Formulations Elastomers Electron Microscope Emulsions Evaluation Future Glycerol Glycolates Goals Hepatic Hepatic artery Hour Image Imaging technology In Vitro Kidney Knowledge Label Left Liver Liver diseases Liver neoplasms Liver parenchyma Lung Malignant Neoplasms Malignant neoplasm of liver Malignant neoplasm of lung Malignant neoplasm of prostate Measurement Measures Medical Device Methods Microspheres Modeling Monitor Neoplasm Metastasis Neuroendocrine Tumors Organ failure Oryctolagus cuniculus Outcome Pancreas Patients Perfusion Phosphate Buffer Polyanhydrides Polymers Porosity Portal vein structure Primary Neoplasm Property Publishing Radiation Radiation therapy Radio Radioactive Radioisotopes Radiolabeled Radionuclide Imaging Radioprotection Rattus Research Risk Scanning Shapes Shunt Device Site Spleen Sprague-Dawley Rats Stomach Surface Survival Rate Technetium 99m Techniques Testing Therapeutic Therapeutic Effect Therapeutic Intervention Time Tissue Engineering Tissues United States Unresectable Vascular blood supply Visceral Work arteriole base biocompatible polymer biodegradable polymer density design dosimetry gastrointestinal improved in vivo internal radiation liver imaging malignant breast neoplasm meetings metastatic colorectal nano outcome forecast particle radiochemical radiotracer response scaffold treatment planning tumor uptake

项目摘要

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.

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。