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

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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.