Imaging and Radiochemistry Core

当前P01应用的中心假设是肿瘤缺氧无创成像的发展将改善实体肿瘤患者的管理，并促进我们对肿瘤缺氧图像的分子和生物学机制的理解。提出了一种整合和比较正电子发射断层成像（PET）和核磁共振成像（NMR）的多模态方法。PET成像方面，我们将利用我们的加速器合成两种有希望的靶向缺氧细胞的放射性示踪剂（124I-IAZG和18F-FMISO）以及相关的反式基因（124I-FIAU和18F-FEAU），并对其进行研究；NMR方面，我们将评估不同的参数指标（如灌注、乳酸水平）作为肿瘤缺氧的替代标志物。因此，成像和放射化学核心C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，既适用于实验室调查的小动物（啮齿动物），也适用于临床调查的人类受试者。在

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.