The meshing of two powerful imaging technologies, such as MR and PET, with the enormous capabilities of genetic engineering and molecular techniques creates an array of possibilities for understanding and imaging cancer. In this proposal for establishing a Pre-ICMIC, we have drawn upon our human resources at Johns Hopkins to create a multidisciplinary group of individuals with diverse skills and expertise, focusing on translating molecular capabilities into imaging possibilities with the single purpose of understanding and curing cancer. The separate subdivisions are organized in a logical progression and parallel, in part, tissue structure and, in part, the course of cancer. These divisional investigations will build on each other starting at the DNA level, to molecular proteins, to carcinogenesis and mitochondrial functioning, to cellular signaling, cell membrane characterization, drug development, transgenic cell and tumor models and finally pre-clinical applications. At each of these subdivisions we envisage a potential feedback into the imaging nucleus. Several of the investigators have interactive collaborative projects with one or more of the other investigators. The synergism generated by the collective skills of this unique group of individuals will lead to significant advances in the understanding of cancer and its treatment. The strengths of our MR Spectroscopy/Imaging and PET capabilities are to image function at the cellular, solid tumor and clinical levels. These capabilities for functional imaging are state-of-the art and include the ability to dynamically image cancer cell invasion, physiology, metabolism and vascularization. We have renowned expertise in three highly significant molecular targets in cancer, the p53 and myc genes and the hypoxia inducible factor HIF-1. Therefore we have sought to combine our expertise in these three targets with our imaging capabilities to answer fundamental and as yet unanswered questions about these targets in cancer progression, invasion and vascularization. The Warburg Effect of increased glycolysis following malignant transformation observed since the 1930's but as yet unexplained will be studied using sophisticated molecular and spectroscopy techniques. Additionally, we propose to develop and characterize MR and PET based gene reporter systems. Finally, we propose to develop fluorescence probes to understand if intracellular lysosomal trafficking is altered in our genetically altered cell lines thereby delineating a mechanism for the secretion of degradative enzymes which promote invasion and metastasis particularly in response to oxygen starvation.
| Mori, Noriko; Delsite, Robert; Natarajan, Kshama et al. (2004) Loss of p53 function in colon cancer cells results in increased phosphocholine and total choline. Mol Imaging 3:319-23 |
| Artemov, Dmitri; Bhujwalla, Zaver M; Bulte, Jeff W M (2004) Magnetic resonance imaging of cell surface receptors using targeted contrast agents. Curr Pharm Biotechnol 5:485-94 |
| Pathak, Arvind P; Gimi, Barjor; Glunde, Kristine et al. (2004) Molecular and functional imaging of cancer: advances in MRI and MRS. Methods Enzymol 386:3-60 |
| Ackerstaff, Ellen; Glunde, Kristine; Bhujwalla, Zaver M (2003) Choline phospholipid metabolism: a target in cancer cells? J Cell Biochem 90:525-33 |
| Artemov, Dmitri (2003) Molecular magnetic resonance imaging with targeted contrast agents. J Cell Biochem 90:518-24 |
| Artemov, Dmitri; Mori, Noriko; Okollie, Baasil et al. (2003) MR molecular imaging of the Her-2/neu receptor in breast cancer cells using targeted iron oxide nanoparticles. Magn Reson Med 49:403-8 |
| Semenza, Gregg L (2003) Angiogenesis in ischemic and neoplastic disorders. Annu Rev Med 54:17-28 |
| Glunde, Kristine; Guggino, Sandra E; Solaiyappan, Meiyappan et al. (2003) Extracellular acidification alters lysosomal trafficking in human breast cancer cells. Neoplasia 5:533-45 |
| Krishnamachary, Balaji; Berg-Dixon, Shannon; Kelly, Brian et al. (2003) Regulation of colon carcinoma cell invasion by hypoxia-inducible factor 1. Cancer Res 63:1138-43 |
| Winnard Jr, Paul; Raman, Venu (2003) Real time non-invasive imaging of receptor-ligand interactions in vivo. J Cell Biochem 90:454-63 |
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