QUANTITATION OF TUMOR GROWTH IN NOVEL CANCER THERAPIES

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[C-11]Thymidine has been shown to be a sensitive and specific agent for observing tumor response to treatment. The radiopharmaceutical for PET imaging is designed to provide quantitative data on tumor DNA synthetic rate. We have incorporated imaging and blood sampling data into kinetic models od DNA metabolism that are used to generate parametric images of thymidine flux rate in tumor. Following our substantial progress in validating this procedure, we will use [C-11]thymidine as a tool to observe tumor response in cancer therapy. In Specific Aim 1a, patients with brain tumors undergoing standard therapy will be studied. The extent of tumor penetration into normal brain will be determined with thymidine flux images. These images will distinguish between abnormalities seen on MR or CT imaging due to blood-brain disruption and proliferative tumor extension. Imaging with [F-18]FDG will provide a comparison between tumor metabolism and proliferation. Specific Aim 2 will measure changes in tumor proliferation in patients with breast cancer undergoing chemotherapy using [c-11]thymidine. Chemotherapeutic agents are highly effective for a percentage of patients but are extremely toxic. The timing and extent of response are unknown. This group of patients will be imaged with [C- 11]thymidine before and after treatment to: 1) profile responders by correlation of thymidine uptake with tumor biopsy and 2) observe the time- course of change in thymidine uptake in responding and on-responding patients. As in Aim 1, FDG images will be obtained at the same timepoints to compare tumor metabolism and proliferation measured with thymidine. Using [C-11]thymidine in association with [F-18]FDG and assays on biopsy material, we will gain valuable insight into the extent and magnitude of response of brain tumors and breast cancer to treatment strategies. PET metabolic imaging with these agents can make comprehensive tumor assessments in vivo over time and will contribute to better patient management as well as better understanding of tumor biology.