HYPOXIA / PERFUSION IMAGING - USING MICROPET WITH (62)CU-PTSM/(62)CU-ATSM

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 肿瘤乏氧已成为一个重要的致瘤因素，因为它限制了肿瘤治疗的反应，如对放疗和化疗的抵抗。 正电子发射断层扫描（PET）是一种很有前途的无创检测肿瘤缺氧的方法。 然而，这种强大的方式是由缺乏可用的，批准的放射性药物的阻碍。Proportional Technologies，Inc. (PTI)已经开发了一种（62）Zn/（62）Cu发生器，其能够合成（62）Cu双（缩氨基硫脲）化合物，包括（62）Cu-PTSM（灌注剂）和（62）Cu-ATSM（缺氧标记物）。 微型发生器的最大优点是它可以以低成本和高灵活性实际提供短寿命的放射性药物。使用微型发生器生产的Cu-62，我们能够更容易和更频繁地进行microPET研究。 （62）Cu的其他优点包括接近100%的正电子产率和9.7分钟的半衰期，这允许良好的图像计数统计和系列研究。 在我们以前的研究中，我们已经评估了（64）Cu-ATSM作为缺氧成像标记物。 我们发现，灌注在Cu-ATSM的缺氧选择性中起重要作用，特别是在高灌注水平的肿瘤中。在这项研究中，我们的目的是使用双放射性药物（62）Cu-PTSM/（62）Cu-ATSM进行灌注标准化缺氧测量。 肿瘤缺氧将首先使用（62）Cu-ATSM缺氧成像 微PET扫描的标记在（62）Cu-ATSM衰减后，将（62）Cu-PTSM引入同一动物以获得灌注图像，随后将其用于计算灌注标准化缺氧。为了验证肿瘤中的灌注水平，我们将在PET扫描后对同一动物进行使用造影剂的microMRI扫描。还将通过双重放射自显影和缺氧免疫组织化学评价缺氧水平。 将进行动物肿瘤放射实验，以将从microPET测量的缺氧水平与对放射治疗的反应相关联。 本研究的目的包括： 1.目的探讨62 Zn/62 Cu微型发生器用于动物microPET研究的可行性。 2.通过比较经灌注剂（62）Cu-PTSM标准化的（62）Cu-ATSM摄取分布与大鼠9 L胶质瘤中EF 5缺氧染色分布，评价（62）Cu-PTSM/（62）Cu-ATSM PET成像准确反映瘤间和瘤内缺氧的能力。 3.评价（62）Cu-PTSM/（62）Cu-ATSM PET预测个体肿瘤对放射治疗反应的能力。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Tumor hypoxia has been an important prognositc factors because it limits the response to tumor treatment, such as resistance to radiation and chemotherapy. Positron emission tomography (PET) is a promising method to detect tumor hypoxia non-invasively. However, this powerful modality is encumbered by the lack of available, approved radiopharmaceuticals. Proportional Technologies, Inc. (PTI) has developed a (62)Zn/(62)Cu generator that is capable of synthesizing (62)Cu bis(thiosemicarbazone) compounds, including (62)Cu-PTSM, a perfusion agent, and (62)Cu-ATSM, a hypoxia marker. The big advantage of the microgenerator is that it can practically deliver short lived radiopharmaceuticals with low cost and high flexibility. With the Cu-62 produced from microgenerator, we are able to perform the microPET study more easily and frequently. Other advantages of (62)Cu include a nearly 100% positron yield and a 9.7 minute half-life, which permits good image count statistics and serial studies. In our previous study, we have evaluated (64)Cu-ATSM as a hypoxia imaging marker. We have found that perfusion plays an important role in hypoxia selectivity of Cu-ATSM, especially in those tumors with high perfusion level. In this study, we aim to conduct perfusion normalized hypoxia measurement using dual radiopharmaceuticals, (62)Cu-PTSM/(62)Cu-ATSM. Tumor hypoxia will be first imaged using (62)Cu-ATSM hypoxia marker from microPET scanning. After the decay of (62)Cu-ATSM, (62)Cu-PTSM will be introduced to the same animal to obtain perfusion image, which will be used later to calculate perfusion normalized hypoxia. To verify the perfusion level in tumor, we will conduct microMRI scanning with contrast agent on the same animal after PET scanning. The hypoxia level will be also evaluated by dual autoradiography and hypoxia immunohistochemistry. Animal tumor radiation experiments will be conducted to correlate the hypoxia level measured from microPET and the response to radiation therapy. The objectives of this study consist of the following: 1. To evaluate the feasibity of performing animal microPET study using 62Zn/62Cu microgenerator. 2. To evaluate the ability of (62)Cu-PTSM/(62)Cu-ATSM PET imaging to accurately reflect inter- and intra-tumoral hypoxia by comparing the distribution of uptake of (62)Cu-ATSM normalized by perfusion agent (62)Cu-PTSM with the distribution of EF5 hypoxia staining in 9L rat gliomas. 3. To evaluate the ability of (62)Cu-PTSM/(62)Cu-ATSM PET to predict individual tumor response to radiation therapy.