We will use [C-11]-labeled thymidine, along with other measures of tumor metabolism (blood flow, blood volume), to test the hypothesis that in vivo measurements of lymphoma metabolism will correlate with response to chemotherapy. These measurements will be obtained before and during therapy in both dogs and humans. We will test the hypothesis that our measurements are valid based on alternative measurements in excised tumors, as well as by replicate measurements. For example, [C-11]- thymidine uptake measured by PET will be compared with direct incorporation into DNA in extracted tissue. One important goal of this work is to determine the relationship between the various metabolic measurements. Initial studies will concentrate on measuring thymidine metabolism, blood flow, and blood volume, since these will be needed to accurately model the delivery and retention of thymidine in the tissue. As they are developed, measurements of energetics as determined by glucose metabolism will be compared to the measurements of thymidine metabolism. Measurements of tumor blood flow and blood volume will also be applied to the study of lymphoma patients being evaluated for therapy with radiolabeled monoclonal antibodies. We have found wide variability in the uptake of radiolabeled antibodies in such patients, and this variability is not explained by differences in antigen density on the tumors. Therefore, we will test the hypothesis that variable tumor blood flow and permeability, as measured with [O-15]-water and[Ga- 68]transferrin respectively, account for the differences in antibody uptake.
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