? ? Molecular imaging has successfully been utilized in the recent past as a technology for imaging various aspects of mammalian physiology. However, the information that can be obtained using these non-invasive modalities is limited since it relies on the expression and imaging of single gene markers. While this information is useful, it can be misleading. For example, markers over-expressed in diseases tissues are also expressed in normal tissues in a spatio-temporal manner making interpretation of the results in a diagnostic setting potentially difficult. Several studies have demonstrated a high degree of both sensitivity and specificity for the identification and molecular classification of diseases by measuring the expression of multiple disease-associated changes in gene expression. The simultaneous over-expression of more than one of these gene markers is, therefore, more predictive of the disease state. Until now, molecular imaging was unable to image more than one marker at a time, requiring either different imaging technologies to be utilized simultaneously or requiring different probes with short biological half-lives to be imaged in rapid succession. The goal of the proposed study is to develop an imaging paradigm that will allow the detection and imaging of multiple over-expressed cancer disease targets at the same time. In the experiments proposed here we will attempt to conjugate these domains to each of three different ligands to simultaneously target and image, via enzyme re-construction in situ, three different molecular imaging targets. Application of this imaging paradigm will be conducted in vivo with animals bearing tumors that express either a subset or all of the biomarkers required for trans complementation. The proposed career development plan will offer the candidate protected time to further develop her research skills by learning new laboratory techniques, taking selective didactic coursework, and expanding her knowledge and experience in the practical conduct of experimentation both in the laboratory and in the clinic under the close supervision of experienced sponsors with input from consultants, collaborators, colleagues, and other faculty within the University. ? ? ?
