Multimodality Biological Imaging of Cancer/Tumor Hypoxia

我们的长期目标是开发非侵入性的多模式成像，以产生三维(3D)人类癌症的生物信息。短期目标是使用核磁共振和正电子发射计算机断层扫描对啮齿动物肿瘤和异种移植的肿瘤生物学和缺氧进行成像。此外，将在相同的肿瘤中直接测量PO2水平，并对肿瘤切片进行表征，为核磁共振和PET图像提供生物学基础。所有图像和肿瘤切片的3D数据集将与在啮齿动物肿瘤和异种移植周围植入的立体定位参考系统进行空间关联。有三个方面的调查。首先，将进行microPET(一种动物扫描仪)的研究：(I)用124I-Annexin V对辐射诱导的细胞凋亡进行活体成像，(Ii)IAZG摄取作为pO2水平的替代，(Iii)比较124IAZG和18Fmiso作为低氧标志物，以及(Iv)评估低氧对FDG摄取的影响。其次，核磁共振研究将包括：(1)通过摄取Gd-DTPA绘制“肿瘤血流”图；(2)用1H核磁共振评估乳酸水平；(3)验证1H和31P核磁共振光谱变化可以预测单个肿瘤对低氧调节的敏感性的假设。第三，将在体内和肿瘤切片中测量/分析同一肿瘤的生物学特征：(I)氧探头的PO2水平，(Ii)Hoescht 33342的血液灌流，(Iii)组织化学分析，(Iv)TUNEL和Annexin V分析的比较，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器系统和图像配准软件进行空间关联，该标记器系统识别多个数据集的图像坐标，图像配准软件改编自我们的放射治疗计划系统中的现有算法。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联系起来。我们相信，这是首次尝试使用空间注册数据集将侵袭性生物端点与来自非侵入性成像的图像特征直接关联。因此，本项目综合了物理学、化学、生物学、工程学和计算机科学，研究肿瘤生物学和缺氧，对癌症的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.