Molecular imaging in regenerative medicine and in T-cell therapies

    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. 

• Parashurama N, Ahn BC, Ito K, Ikeno F, Ziv K, Swanson J, Merk D, Chung J, Lyons J, Yerushalmi D, Teramoto T, Kosuge H, Dao C, Ray P, Patel M, Chang Ya-fang, Bhaumik S, Yaghoubi S, Willmann J, McConnell M, Dash R, Brinton T, Yang P, Yock P, Robbins RC, Gambhir SS. Molecular imaging of cardiac cell transplantation Part I; Reporter gene design, characterization, and optical in vivo imaging. Radiology. 2016 Sep; 280(3):826-36. Citations: 3
• Parashurama N, Ahn BC, Ito K, Ikeno F, Ziv K, Swanson J, Merk D, Chung J, Lyons J, Yerushalmi D, Teramoto T, Kosuge H, Dao C, Ray P, Patel M, Chang Ya-fang, Bhaumik S, Yaghoubi S, Willmann J, McConnell M, Dash R, Brinton T, Yang P, Yock P, Robbins RC, Gambhir SS. Molecular imaging of cardiac cell transplantation Part II ; In vivo large animal imaging with PET-CT and MRI. Radiology. 2016 Sep; 280(3):815-25. Citations: 3
• Parashurama N*, Lobo NA, Ito K, Mosely A, Habte F, Smith BR, Lam J, Weissman I, Clarke MF, Gambhir SS. Remodeling of endogenous mammary epithelium by breast cancer stem cells. Stem Cells. 2012 Oct; 30(10): 2114-27. (Featured as Cover Article) Citations: 19
• Ahn BC*, Parashurama N*, Ramasamy P, Patel M, Ziv K, Bhaumik S, Yaghoubi SS, Gambhir SS. Noninvasive reporter gene imaging of human Oct4 (pluripotency) dynamics during the differentiation of embryonic stem cells in living subjects. Mol Imaging Biol. 2014 May 21. Citations: 9

• Matthew Willadsen (MS)
• Iven Yarovoy (MS)
• Zachary Dickman (MS)
• Tala Mon (MS)
• Jillian Annis (MS)