Core A: Bioanalysis

项目总结 生物分析核心的目的是提供集中的生物分析支持。这一核心将促进 分析的标准化和效率，并提供可共享和比较的基本信息 该计划中的所有三个项目。这一新的重组核心将为以下方面提供支持 现有的用于临床的光动力增敏剂的临床和临床前组织和生物液分布 和临床前研究以及任何新开发的用于光动力疗法(PDT)的PS。这些数据是必不可少的 用于解释患者和动物模型中的光动力疗法活动。项目2中描述的PSS在 可见光谱的红色或近红外区域，是强荧光的。因此，标准化检测 已经开发出了利用这些化合物的光物理性质的方法。《生物分析》 CORE将评估选定化合物在小鼠体内的肿瘤组织滞留情况。 使用荧光分光光度法(如果可能，液体闪烁计数法)计算人类肿瘤的来源 检测放射性同位素标记的[14C]光敏剂)。将使用荧光分光光度法来 测定人血清和溶解的活检和手术标本中的光敏剂水平。核心A将 检测SADA(血清碱性DNA酶)作为预测PDT的循环生物标志物 头颈部患者的反应。这将包括从患者身上常规采集血液，然后是 SADA活性的标准分光光度分析。核心还将收集血液，隔离和储存 从我们的头颈部患者身上提取免疫细胞进行分析。具体地说，个别项目已确定 支持临床和转化科学研究的多个领域。核心的具体目标 是：1)测定患者组织和生物液中的光敏剂水平；2)收集、分离和 存储患者的免疫细胞以供后续分析，3)测量非侵入性的循环生物标记物 (血清碱性DNA酶)和4)测量光敏剂在异种头部移植小鼠体内的保留情况 和颈部肿瘤。

PROJECT SUMMARY The purpose of the Bioanalysis Core is to provide centralized bioanalysis support. This Core will promote standardization and efficiency of analysis and provide essential information that can be shared and compared across all three Projects in the Program. This new, reorganized Core will provide support for all aspects of clinical and preclinical tissue and biofluid distribution of existing photodynamic sensitizers (PS) used in clinical and preclinical studies and any newly developed PS for photodynamic therapy (PDT). These data are essential for interpreting PDT activity in patients and animal models. PSs described in Project 2 have absorption in the red or NIR regions of the visible spectrum and are strongly fluorescent. As such, standardized detection methods have been developed to exploit the photophysical properties of these compounds. The Bioanalysis Core will evaluate the tumor tissue retention of select compounds in mice bearing established and patient- derived human tumors using fluorescence spectrophotometry (and, if possible, liquid scintillation counting to detect radioisotopically-labeled [14C] photosensitizers). Fluorescence spectrophotometry will be used to determine photosensitizer levels in human serum and solubilized biopsy and surgical specimens. Core A will measure SADA (serum alkaline DNase) as a circulating biomarker that has the potential to predict PDT response in head and neck patients. This will involve routine blood collection from patients followed by standard spectrophotometric analysis of SADA activity. The Core will also collect blood and isolate and store immune cells from our head and neck patients for analysis. Specifically, the individual Projects have identified a number of areas of support for both clinical and translational science studies. The specific aims of the Core are: 1) to determine photosensitizer levels in tissues and biological fluids of patients, 2) to collect, isolate and store immune cells from patients for subsequent analysis, 3) to measure noninvasive, circulating biomarker (serum alkaline DNase) and 4) to measure the retention of photosensitizers in mice bearing xenografted head and neck tumors.