Multimodality Biological Imaging of Cancer/Tumor Hypoxia

我们的长期目标是开发非侵入性多模态成像，以三维（3D）形式产生人类癌症的生物信息。 短期目标是使用NMR和PET对啮齿动物肿瘤和异种移植物中的肿瘤生物学和缺氧进行成像。 此外，将直接测量相同肿瘤中的pO 2水平，并对肿瘤切片进行表征，为NMR和PET图像提供生物学基础。 图像和肿瘤切片的所有3D数据集将与植入啮齿动物肿瘤和异种移植物周围的立体定位参考系统在空间上相关。 有三个调查领域。首先，将进行microPET（动物扫描仪）研究：（i）用124 I-膜联蛋白V对辐射诱导的细胞凋亡进行体内成像，（ii）将IAZG摄取作为pO 2水平的替代物，（iii）将124 IAZG与18 Fmiso作为缺氧标志物进行比较，以及（iv）评估缺氧对FDG摄取的影响。其次，NMR研究将包括：（i）通过Gd-DTPA摄取绘制“肿瘤灌注”图，（ii）用1H NMR评估乳酸水平，以及（iii）检验1H和31 P NMR光谱变化可以预测个体肿瘤对缺氧调节的易感性的假设。第三，将在体内和肿瘤切片中测量/分析相同肿瘤的生物学特征：（i）用氧探头测量pO 2水平，（ii）用Hoescht 33342进行血液灌注，（iii）组织化学分析，（iv）比较TUNEL和膜联蛋白V测定，以及（v）荧光板放射自显影。上述将使用可植入立体定位标记系统和图像配准软件进行空间相关，所述可植入立体定位标记系统识别多个数据集的图像坐标，所述图像配准软件从我们的放射治疗计划系统中的现有算法进行调整。重要的是所有3D数据集的空间相关性，从而将生物属性与图像特征相关联。 我们相信这是首次尝试使用空间配准的数据集将侵入性生物终点与来自非侵入性成像的图像特征直接关联。 因此，本项目融合物理、化学、生物、工程和计算机科学，研究肿瘤生物学和缺氧，对癌症诊断和治疗具有相当大的意义。

Our long range goal is to develop non-invasive multi- modality imaging that yields biological information of human cancers in 3-dimensions (3D). The short-term objectives are to use NMR and PET for imaging tumor biology and hypoxia in rodent tumors and xenografts. In addition, pO2 levels will be directly measured in the same tumors, and tumor sections characterized to provide a biological basis for the NMR and PET images. All the 3D data sets of images and tumor sections will be spatially correlated with a stereotaxic reference system implanted around the rodent tumors and xenografts. There are three areas of investigation. First, microPET (an animal scanner) studies will be performed: (i) in vivo imaging of radiation-induced apoptosis with 124I- Annexin V, (ii) IAZG uptake as a surrogate of pO2 level, (iii) comparing 124IAZG with 18Fmiso as hypoxia markers, and (iv) assessing the effect of hypoxia on FDG uptake. Second, NMR studies will include: (i) mapping "tumor perfusion" by Gd-DTPA uptake, (ii) assessing lactate level with 1H NMR, and (iii) testing the hypothesis that 1H and 31P NMR spectral changes can predict the susceptibility of individual tumors to hypoxia- modulation. Third, biological features will be measured/analyzed in vivo and in tumor sections for the same tumors: (i) pO2 level with an oxygen probe, (ii) blood perfusion with Hoescht 33342, (iii) histochemical analysis, (iv) comparison of the TUNEL and Annexin V assays, and (v) phosphor plate autoradiography. The above will be spatially-correlated using an implantable stereotaxic marker system that identifies the image coordinates of the multiple data-sets and image registration software adapted from existing algorithms in our radiotherapy treatment planning system. Of significance is the spatial correlation of all the 3D data sets, thus relating biological attributes to image features. We believe that this is the first attempt to directly correlate invasive biological endpoints with image features from non- invasive imaging using spatially registered data-sets. Thus, this project integrates physics, chemistry, biology, engineering and computer sciences to study tumor biology and hypoxia, with considerable significance for cancer diagnosis and treatment.