ANIMAL CORE: PHARMACOKINETICS, IMAGING AND THERAPY

核心D是动物核心：药代动力学、成像和治疗。该核心的主要功能是支持项目1中使用的临床试剂在动物模型中的质量控制研究，项目2中开发的肿瘤靶向放射性标记构建体的开发，以及项目3中基于抗体的免疫治疗剂在许多模型系统中的开发。将在生物分布和治疗研究中以及通过使用COH提供的先进动物成像仪器（如适用）对药物进行评价。具体职能是：1）提供所需的设施和专业知识，以评估基于抗体的构建体在小动物中的生物分布和成像;以及2）进行研究，以分析基于抗体的放射性标记构建体和免疫治疗剂在模型系统中的药代动力学和治疗功效。核心还将评价在核心C中制备的用于项目1和3的临床使用的材料。 核心D是项目1、2和3的一个重要组成部分。所有抗体构建体将在转化到临床之前进行体外和体内评价。体内分析将作为本核心的一部分，使用核心人员的专业知识进行。动物生物分布和成像研究将由核心人员在各个项目的帮助下进行。体内研究将需要研究动物护理委员会的批准，并将在Pan/in大楼的City of Hope动物资源中心进行。本核心将评价项目2中开发的[111] In、[125] I、[131] I、[177] Lu、[90] Y、[64] Cu或[124] I标记后的多步靶向方法、肽接头和新型抗体螯合物缀合物。

Core D is the Animal Core: Pharmacokinetics, Imaging and Therapy. This core's main function is to support the quality control studies in animal models of the clinical reagents used in Project 1, the development of the tumor targeted radiolabeled constructs developed in Project 2 and the antibody based immunotherapeutics in Project 3 in a number of model systems. The agents will be evaluated in both biodistribution and therapy studies as well as by using the advanced animal imaging instrumentation available at the COH, where appropriate. The specific functions are: 1) To provide the needed facilities and expertise for evaluating the biodistribution and imaging of antibody based constructs in small animals; and 2) To perform studies to analyze the pharmacokinetics and therapeutic efficacy of antibody based radiolabeled constructs and immunotherapeutics in model systems. The Core will also evaluate materials prepared in Core C for clinical use in Projects 1 and 3. Core D is a critical component of Projects 1, 2 and 3. All antibody constructs will be evaluated in vitro and in vivo prior to translation into the clinic. The in vivo analysis will be performed as part of this Core using the expertise of the Core's personnel. Animal biodistribution and imaging studies will be performed using the Core personnel with help as needed from the individual projects. The in vivo studies will require approval by the Research Animal Care Committee and will be performed in the City of Hope Animal Resource Center in the Pan/in building. This Core will evaluate the multi-step targeting methods, peptide linkers and novel antibody chelate conjugates developed in Project 2 after labeling with [111]In, [125]I,[131]I, [177]Lu, [90]Y, [64]Cu, or [124]I.