) With the advent of a better understanding of cell and biological processes at a molecular level coupled with the development of new biological reagents and probes, and recent developments and improvements in imaging technology, it is appropriate to focus attention on bringing together these advances. More importantly, it is recognized that molecular and cell-based imaging can impact directly on cancer treatment and diagnosis, and that the development and testing of new molecular-based therapies would benefit substantially from advances in our ability to image specific molecular and cell processes. In the last few years, several groups in this country (including several at MSKCC) have begun to integrate these diverse disciplines with some success. For example, multi-disciplinary interactions at MSKCC has led to the demonstration of the feasibility for imaging transgene expression in vivo, and the use of noninvasive """"""""reporter gene"""""""" imaging is being expanded to include specific cell processes at a molecular level. This theme, the translation and implementation of molecular and cell-based imaging into the clinical arena, is a strength of the MSKCC program and this proposal, and this theme is carried throughout the structure and individual components of this proposal The vision of this proposal through the interaction of existing disciplines at MSKCC, is: 1) to develop noninvasive imaging paradigms that reflect specific cellular/molecular processes (such as endogenous gene expression) and protein-protein interactions within specific signal transduction pathways; 2) imaging the selective amplification of therapeutic genes; 3) monitoring the trafficking and targeting of genetically modified T cells; 4) imaging the growth and vascularization of tumor spheroids in vivo; 5) the use NMR spectroscopy and PET imaging to optimize chemotherapy and gene therapy; 6) imaging the anti-tumor effects of ancamycins ins at a molecular and cellular level; 7) the application of metabolic PET imaging and molecular-pathology in the assessment of disease progression anc response in patients with prostate cancer; 8) combining dosimetiry estimates and imaging of molecular targetins with 86Y/90Y- labeled anti-CD 19 and anti-CD2O antibodies in patients. The coordinating theme of this proposal is the potential for molecular and cell-based imaging to have a direct impact on the treatment and diagnosis of cancer, and to provide new research opportunities that will further our inderstanding of cancer, cancer progression and response to therapies targeted to specific molecular processes.
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