Phase I trials of cancer vaccines are typically performed in patients with measurable, often advanced disease. Vaccine efficacy is judged by monitoring changes in tumor size after the initiation of vaccine therapy. Using this study population, advanced stage cancer patients, few cancer vaccine trials have shown clinical efficacy. Since change in size of the tumor is a relatively late consequence of disease response or progression, and vaccine therapy may have a different effect on tumor growth or biology than chemotherapy, i.e. more cytostatic than cytotoxic, monitoring size is a crude way of assessing response. Radiotracer methods such as positron emission tomography (PET) can measure the physiologic and biochemical changes associated with an anti-tumor response, such as the local change in cellular proliferation or glucose metabolism. Although these approaches have been validated in patients receiving cytotoxic chemotherapy, their application to vaccine therapy involves potentially confounding effects, such as the possibility of increased metabolism associated with the immune response. In this pilot project we propose studies in an animal model for vaccine therapy to test and validate these promising methods of vaccine response evaluation. Perhaps, novel methods of imaging will allow some early assessment of vaccine clinical efficacy prior to the institution of large-scale trials. Our hypothesis is that the quantitative changes in cellular proliferation measured by labeled thymidine will accurately reflect tumor response early in the course vaccine therapy, even if that response is cytostatic. A decline in FDG uptake over the course of treatment may also indicate a tumor response; however, there may an early increase in metabolism associated with immune response at the tumor site. The specific aims of this pilot project are to: (1) Determine whether changes in FDG and thymidine uptake correlate with tumor growth or regression in a murine breast cancer model responsive to antigen specific immunization. (2) Determine whether changes in FDG and thymidine uptake predict tumor shrinkage or growth at an earlier time point than standard measures of tumor size. (3) Determine if an increase in FDG uptake tumor occurs with the initiation of an immune response at the tumor site. We anticipate that the studies described here will lead to a pilot Phase I trial of techniques in patients with measurable tumors undergoing HER2 vaccination.