Imaging and Radiochemistry Core

当前P01申请的中心假设是，肿瘤缺氧的无创成像的开发将改善实体瘤患者的管理，并促进我们对肿瘤缺氧图像背后的分子和生物学机制的理解。提出了一种多模态方法，集成和比较正电子发射断层扫描（PET）和核磁共振（NMR）成像。对于PET成像，将使用我们的回旋加速器合成并研究两种有前途的特异性靶向缺氧细胞的放射性示踪剂（124 I-IAZG和18 F-FMISO）和相关转基因（124 I-FIAU和18 F-FEAU），对于NMR，将评估不同的参数指标（例如灌注，乳酸水平）作为肿瘤缺氧的替代标志物。因此，核心C（成像和放射化学核心）的功能是为研究项目和其他核心提供最先进的体内和离体成像能力和正电子发射放射性示踪剂-用于实验室研究中的小动物（啮齿动物）和临床研究中的人类受试者。在 除了提供用于临床研究的新型PET-CT扫描仪外，我们的Core还提供一系列最先进的小动物成像和支持系统- microPET、MS生物发光和荧光光学成像、X-SPECT microSPECT-microCT、microCAT II microCT、4.7-T 40-cm孔径和7.0-T 31-cm Bruker NMR系统、高分辨率荧光板数字放射自显影和数字显微镜。我们计划项目的一个关键组成部分，特别是这个核心，是我们正在开发一种实用的、普遍适用的方法-包括所有必要的硬件和软件-用于真正的多模态以及动物研究中的模态内图像配准。我们正在开发的图像配准方法提供了在宽“动态范围”内精确图像配准的能力--从超高分辨率数字放射自显影（< 100 μ m）和组织切片图像（< 10 μ m）到较粗分辨率（约100 μ m（NMR，microCT）到约1，000 μ m） μ m（microPET，microSPECT））体内图像。通过直接比较不同区域的明确配准图像进行确证 这些多种形式不仅将加速新示踪剂和新成像和图像分析方法的验证，而且可以 还提供了独特的，治疗上重要的见解肿瘤的基础生物学（如相互作用的影响， 因素如葡萄糖代谢、血流、缺氧、乳酸水平等）关于肿瘤对治疗的反应。

The central hypothesis of the current P01 Application is that the development of non-invasive imaging of tumor hypoxia will lead to improved management of solid-tumor patients and advance our understanding of the molecular and biological mechanisms underlying tumor hypoxia images. A multi-modality approach, integrating and comparing positron emission tomography (PET) and nuclear magnetic resonance (NMR) imaging, is proposed. For PET imaging, two promising radiotracers that specifically target hypoxic cells (124I-IAZG and 18F-FMISO) and relevant trans-genes and (124I-FIAU and 18F-FEAU) will be synthesized with our cyclotron and investigated, and for NMR, different parametric indices (e.g. perfusion, lactate levels) will be evaluated as surrogate markers of tumor hypoxia. The function of Core C, the Imaging and Radiochemistry Core, is to therefore provide state-of-the-art in vivo and ex vivo imaging capabilities and positron-emitting radiotracers - both for small animals (rodents) in laboratory investigations and for human subjects in clinical investigations - for the Research Projects and the other Cores. In addition to the availability of new PET-CT scanners for clinical studies, our Core provides an array of state-of-the art small-animal imaging and support systems - microPET, MS bioluminescence and fluorescence optical imaging, X-SPECT microSPECT-microCT, microCAT II microCT, 4.7-T 40-cm bore and 7.0-T 31-cm Bruker NMR systems, high-resolution phosphor-plate digital autoradiograph, and digital microscopy. A key component of our Program Project and, in particular, this Core is our ongoing development of a practical, generally applicable method - including all necessary hardware and software - for truly multi-modality as well as intra-modality image registration in animal studies. The image registration method we are developing provides the capability of precise image registration over a broad "dynamic range" - from ultra-high-resolution digital autoradiograms (< 100 (mu m) and histological-section images (< 10 mu m) to coarser-resolution (approximately 100 mu m (NMR, microCT) to approximately 1,000 mu m (microPET, microSPECT)) in vivo images. Corroboration by direct comparison of unambiguously registered images across these multiple modalities will not only expedite validation of new tracers and new imaging and image-analysis methods but may also provide unique, therapeutically important insights into the underlying biology of tumors (such as the effect of interacting factors such as glucose metabolism, blood flow, hypoxia, lactate levels, etc.) on tumor response to therapy.