Molecular imaging uses a wide variety of modalities to image biological events in living subjects, including small animals, large animals, and patients.
The aging population an increase in chronic diseases and organ failure, and a shortage of sufficient organs for transplantation have exacerbated the need for alternate therapeutic approaches. The field of regenerative medicine, comprised of biomedical scientists, chemical and biological engineers, and physicians, promises to replace damaged or diseased organs. Stem cells and cell-based therapies, engineered tissues, and biomaterials are the mainstay of these therapies. Thus, regenerative medicine is predicated upon the manipulation, use, and transplantation of complex cellular/tissue systems. Consequently, when used therapeutically these have unpredictable behavior, due to transplant factors (delivery, cell fate) and host factors (extent of disease, individual genome). The compounding of these effects results in a great risk of treatment failure, and not surprisingly, efficacy in clinical trials has been hard to demonstrate with accompanying hurdles to clinical translation. Tools that can better decipher biological behavior in preclinical models, and enable individual monitoring in patients, could greatly improve therapy selection, dosing, delivery approaches, and better link disease state, therapeutic choice, and outcome. We are currently integrating stem cell biology projects with endoderm, liver, and pancreas together with reporter gene-based molecular imaging to better understand the in vivo fate of these cells.
We are pursuing several approaches to integrate molecular imaging in regenerative medicine. Cell-based immunotherapies, in particular, have recently generated enormous excitement for their efficacy in cancer treatments. The basis of these therapies is that lymphocytes in the blood stream called T-cells, which are specialized for cell killing, can traffic through the blood and target and destroy primary and metastatic tumors. Although T-cell therapies have reached the clinical stage, and have recently demonstrated increased efficacy, numerous questions remain. We believe imaging tools can address many of these important questions in immunotherapies. We retrovirally labelled antigen specific T cells with reporter genes, and are tracking them in murine models of highly metastatic ovarian cancer. Based on the data, we are developing a hypothesis of how T cells home to specific sites in tumors, whether metastatic or primary. We are investigating variables such as cell dose, vaccine-based boosting with an oncolytic virus, size of tumor, and understanding individual events at tumor sites to better develop T cell therapies in patients. This is a collaboration with Dr. Kunle Odunsi at the Center for Immunotherapy, and the translational imaging core, at Roswell Park Cancer Institute.