Tracking stem cell therapy in the myocardium: applications of positron emission tomography

The introduction of stem cells and/or progenitor cells into damaged myocardium has promising therapeutic potential in ischemic heart diseases and dilated cardiomyopathy. However, understanding the biologic mechanisms and the outcomes of transplanted cells during cardiac regenerative therapy remains mostly limited to histological assessment. Positron emission tomography (PET) is a sensitive molecular imaging modality that can non-invasively assess stem cell retention, survival, and function after transplantation. Two radiolabel approaches have been explored to implement PET: 1) direct cell labeling with a radionuclide; and 2) reporter gene-based cell labeling. Direct cell labeling has previously been used for early tracking of transplanted stem cells into the myocardium in several therapeutic clinical trials. Stem cells can also be labeled after transfection with a reporter gene, which can subsequently be visualized by using a PET reporter probe that binds to the reporter gene, therefore allowing serial in vivo evaluation of cell viability and proliferation in long-term follow-up studies. Recently, some studies successfully used this method to visualize implanted stem cells by PET imaging in animals. With the projected rapid growth of cell therapy for heart disease, PET is expected to play a major role in monitoring relevant changes that occur at every stage in cardiac regenerative therapy. These two cell tracking approaches used for PET imaging are reviewed here and compared against other imaging modalities.