CLINICAL IMAGING AND RADIATION DOSIMETRY

CORE A CORE董事：Bding，James首席调查员：Raubitschek，Andrew 说明： 核心A的总体目标是提供最先进的成像、辐射剂量测定和 新型放射性标记单抗临床试验的药代动力学模拟支持 其他免疫治疗剂。核心的主要责任是帮助主要调查人员 我们的许多研究项目都在他们的临床研究方案中优化了成像的使用。为此，核心 将(A)确定和实施目前定量成像、内部剂量测定的最佳做法 使用放射性同位素，以及使用成像来评估和预测肿瘤对治疗的反应；和(B) 根据需要进行研究/开发，以优化临床研究方案中成像的使用。这个 核心A团队还将为仪器校准和临床扫描采集提供质量保证。 核心A由两位经验丰富的成像物理学家/辐射剂量学家/动力学模型师领导，还 包括一名功能成像临床应用方面的放射科专家、一名图像分析师/程序员、一名 数据库管理员/开发人员和成像研究技术人员。现代临床的全面补充 提供成像设备，包括SPECT-CT和PET-CT(在赠款开始时)。另一个 关键设备资源是一个集图像处理、显示和分析为一体的系统，致力于 临床研究。 在药代动力学和辐射剂量学领域，核心将(A)继续进行量化 放射免疫治疗临床试验的图像分析和剂量计算；(B)补充 SPECT-CT平面成像提高肿瘤和正常组织放射性测量的准确性 (C)采用基于体素的3D方法来估算辐射吸收剂量；(D)评估 SPECT-CT与基于体素的剂量学对估算的肿瘤吸收剂量相关性的影响 和反应；(E)评价使用动力学模型来区分影响肿瘤的因素 (F)评估抗血管生成药物阿瓦斯丁对肿瘤摄取BIT单抗的影响。 RIT MABS。该核心还将在评估治疗反应方面作出重大努力。 (A)建立一个形象反应评估小组；(B)实施质量保证方案 用于测量肿瘤对治疗的反应；和(C)评估功能/代谢指标的使用 在我们的临床治疗试验中测量肿瘤反应(PET/[18F]FDG)。 核心A直接支持项目1和项目3，这两个项目共同包含所有建议的临床试验 在接下来的五年。核心A提供成像物理、药代动力学建模和辐射剂量测定 支持核心D(动物核心)；核心A还主要负责将成像方面的进展转化为 在动物身上发展成临床使用。核心A通过开发建模间接支持项目2 将有助于预靶向RIT的临床试验设计的方法学。核心A获得来自 核心E(生物统计学)在实验设计和数据管理领域。

Core A core Director: Bading, James Principal investigator: Raubitschek, Andrew DESCRIPTION: The overall objective of Core A is to provide state-of-the-art imaging, radiation dosimetry and pharmacokinetic modeling support for clinical trials of novel radiolabeled monoclonal antibodies (MAbs) and other immunotherapeutic agents. The primary responsibility of the Core is to help the principal investigators of our research projects optimize the use of imaging in their clinical study protocols. To that end, the Core will (a) identify and implement current best practices for quantitative imaging, dosimetry of internally administered radioisotopes, and the use of imaging to assess and predict tumor response to therapy; and (b) perform research/development as needed to optimize the use of imaging in the clinical study protocols. The Core A team will also provide quality assurance for instrument calibration and clinical scan acquisition. Core A is led by two highly experienced imaging physicist/radiation dosimetrist/kinetic modelers and also ncludes a radiologist expert in clinical applications of functional imaging, an image analyst/programmer, a data base administrator/developer and an imaging research technician. A full complement of modern clinical maging equipment is available, including SPECT-CT and PET-CT (by the initiation of the grant). Another key equipment resource is a well-integrated image processing, display and analysis system dedicated to linical research studies. In the area of pharmacokinetics and radiation dosimetry, the Core will (a) continue to perform quantitative image analysis and dosimetric calculations for clinical radioimmunotherapy (BIT) trials; (b) supplement planar imaging with SPECT-CT to improve accuracy of radioactivity measurements in tumors and normal organs; (c) implement a 3D, voxel-based method for estimating radiation absorbed dose; (d) evaluate the impact of SPECT-CT and voxel-based dosimetry on the correlation between estimated tumor absorbed dose and response; (e) evaluate the use of kinetic modeling to differentiate among the factors affecting tumor uptake of BIT MAbs; and (f) evaluate the effect of the anti-angiogenesis agent Avastin on tumor uptake of RIT MAbs. The Core will also undertake a major effort in the area of assessment of treatment response by (a) establishing an image response assessment team (IRAT); (b) implementing a quality assurance program for measurements of tumor response to treatment; and (c) evaluating the use of a functional/metabolic measure of tumor response (PET/[18F]FDG) in our clinical therapy trials. Core A directly supports Project 1 and Project 3, which together contain all of the clinical trials proposed for the next five years. Core A provides imaging physics, pharmacokinetic modeling and radiation dosimetry support to Core D (Animal Core); Core A also has primary responsibility for translating imaging advances developed in animals into clinical use. Core A indirectly supports Project 2 by developing modeling methodology that will contribute to clinical trial design for pretargeted RIT. Core A receives support from Core E (Biostatistics) in the areas of experimental design and data management.