Multimodality Biological Imaging of Cancer/Tumor Hypoxia

我们的长期目标是发展非侵入性的多模态成像，在三维（3D）中产生人类癌症的生物信息。短期目标是利用核磁共振和PET成像肿瘤生物学和缺氧在啮齿动物肿瘤和异种移植物。此外，pO2水平将在同一肿瘤中直接测量，并对肿瘤切片进行表征，为NMR和PET图像提供生物学基础。所有图像和肿瘤切片的三维数据集将与植入在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。调查有三个方面。首先，将进行微pet（一种动物扫描仪）研究：(i)使用124I- Annexin V进行辐射诱导的细胞凋亡的体内成像，（ii） IAZG摄取作为pO2水平的替代品，（iii）比较124IAZG与18Fmiso作为缺氧标志物，（iv）评估缺氧对FDG摄取的影响。其次，核磁共振研究将包括：(i)通过Gd-DTPA摄取来绘制“肿瘤灌注”图，（ii）通过1H NMR评估乳酸水平，以及（iii）验证1H和31P NMR光谱变化可以预测个体肿瘤对缺氧调节的敏感性的假设。第三，将在同一肿瘤的体内和肿瘤切片中测量/分析生物学特征：(i)氧探针检测pO2水平，（ii） Hoescht 33342血液灌注，（iii）组织化学分析，（iv） TUNEL和Annexin V检测的比较，以及(V)荧光板放射自显影。以上将使用可植入的立体定位标记系统进行空间关联，该系统识别多个数据集的图像坐标和图像配准软件，这些软件采用了我们放射治疗计划系统中现有的算法。重要的是所有三维数据集的空间相关性，从而将生物属性与图像特征联系起来。我们认为，这是第一次尝试直接将侵入性生物端点与使用空间注册数据集的非侵入性成像的图像特征联系起来。因此，本项目将物理、化学、生物、工程和计算机科学相结合，研究肿瘤生物学和缺氧，对癌症的诊断和治疗具有重要意义。

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.