This application, for a Research and Research Infrastructure "Grand Opportunities" (GO) grant (RFA- OD-09-004) will focus on "Comparative Oncology Research" and requests funds for a unique state of the art PET insert for an MR animal scanner which will be used by numerous biomedical research laboratories as an open scientific resource, with a major impact on translational oncology research. There are 30 principal investigators and 37 peer reviewed research projects supported by this application including projects from 9 institutions outside MSKCC. Simultaneous acquisition of PET and MR data will be used for studies of novel dual MR-PET contrast agents, concurrent kinetics, biochemical studies of metabolism, and to study the distribution of labeled antibodies and the effects of hypoxia, tumor perfusion heterogeneity on uptake, targeting and efficacy. Many physiological phenomena (such as hypoxia, perfusion, pharmacokinetics) undergo acute changes, vary from animal to animal, and contrast/radiotracer agent uptake and distribution may depend on different time varying physiological parameters so simultaneous acquisition is critical. Our collaboration with Dr. Cherry envisages construction of a PET insert for MSKCC, and we will provide NMR (lactate pulse sequences, quantitation, radiofrequency coils) and chemistry expertise. We will evaluate the effect of the PET insert on MR image and spectral quality at both 4.7T and 7T and the effect of both magnets on PET performance and provide this data to Dr. Cherry. We will improve and develop novel pulse sequences for lactate detection and imaging which will be used frequently with concurrent fluorodeoxyglucose (FDG) PET scanning since both are measuring different aspects of glycolysis and are markers of prognosis. A critical development will be an isolation chamber in order to allow investigators from many institutions to use the imaging equipment and minimize the risk of cross contamination of animals from different institutions. This chamber is designed to isolate the animal from the scanner and will have ports for respiratory, temperature and cardiac monitoring to decrease morbidity and improve image quality, in addition to a port for inhalation anesthesia and other gases. MSKCC is a world leader in development and translation of radiolabeled small molecules, peptides and antibodies for the imaging and therapy of cancer. We have access to a broad gamut of radionuclides for PET studies and the chemistry expertise to dual label them with 19F, Fe or Gd to produce agents that can be visualized by both MR and PET. We will develop the isolation chamber, lactate detection methods, and novel dual modality contrast agents prior to the delivery of the PET insert for immediate use upon delivery. The MR-PET scanner will support 37 different projects that will yield significant benefit form this research. This project will be started immediately if funded and enhance multidisciplinary research and interactions between investigators of broadly different background, thereby leading to new breakthroughs in cancer care. PUBLIC HEALTH RELEVANCE: Relevance This application, for a Research and Research Infrastructure "Grand Opportunities" (GO) grant (RFAOD- 09-004) will focus on "Comparative Oncology Research" and requests funds for a unique state of the art Positron Emission Tomography (PET) insert for an MR animal scanner which will be used by numerous biomedical research laboratories as an open scientific resource, with a major impact on translational cancer research.