Sarcoma in adults is a disease with highly variable behavior and response to treatment. While high grade tumors respond well to pre-surgical chemotherapy and surgical resection, tumors of low and intermediate grades have variable response. Additionally, high levels of heterogeneity in sarcomas can render needle biopsy for diagnosis inadequate. These variable areas of tumor also respond differently to chemotherapy. To aid in treatment planning for individual patients, knowledge of tumor grade, heterogeneity in biologic activity, and response to chemotherapy would be of great benefit to the oncologist. In this proposal, we will address these clinical problems using positron emission tomography (PET) to non- invasively assess tumor response to treatment. Using [F-18] fluorodeoxyglucose (FDG) we will perform quantitative imaging studies on patients to determine the tumor local FDG metabolic rate (FDGMR). We hypothesize that FDGMR will be a more sensitive indicator of treatment response and tumor grade compared with histology than a simple uptake ratio. To further assess tumor grade and heterogeneity, we will use [C- 11]thymidine as a marker for quantitating tumor growth (DNA synthetic rate) in patients prior to treatment. Our hypothesis is that tumor response to cytotoxic drugs can be predicted from [C-11]thymidine utilization, a measure of cell cycle activity in conjunction with FDG, a measure of energy metabolism, conventional histology, flow cytometry and use of immunocytochemical cell proliferation markers. These studies will be performed in patients with all sarcoma tumor grades at the time of disease diagnosis and staging. This proposal focuses on important clinical questions relevant to sarcoma patient management using PET. It will provide insight on the utility of imaging FDG, thymidine and labeled chemotherapeutic agents is solid tumors, but the experience gained will be applicable to other solid tumors.
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