| Cellular therapeutics, such as cellular cardiomyoplasty (CCM), involves the use of cells to treat disease and is currently being investigated as a means to favorably affect cardiac tissue remodeling that occurs following myocardial infarction (MI). Such tissue remodeling has deleterious effects leading to increased morbidity and mortality in MI patients. Of interest in CCM research, is the understanding of the in vivo survival, differentiation, and engraftment of transplanted cells in a non-invasive, quantitative, and serial manner. In this thesis, it has been established that Indium-111 imaging with Single Photon Emission Computed Tomography (SPECT) in a canine model of MI can be used as an in vivo marker of transplanted bone marrow cell viability within the first two weeks of intramyocardial transplantation. As an imaging agent to assess viability, key findings demonstrated that: (1) 111In clearance kinetics were markedly different between dead and viable cells in infarcted and normal myocardium; (2) SPECT image analysis should not be confounded by non-specific uptake of released label in surrounding myocardial tissue; (3) a model of transplanted cell survival using dead cell and leakage clearance kinetics was developed presenting a method to calibrate apparent clearance kinetics with the true clearance kinetics; (4) injections into the subendocardium or subepicardium do not significantly affect 111In leakage clearance kinetics; (5) safe cellular levels of 111In do not prevent processes of cellular proliferation and differentiation in canine stem/progenitor cell populations;;Keywords. Single Photon Emission Computed Tomography (SPECT); Indium-111; myocardial infarction; canine model; cell transplantation; cell survival;This novel method has been created in an opportunistic niche as reporter gene/probe technology is not ready for the clinic, but is the first to establish itself as a clinically feasible, non-genetic alternative to image transplanted cell survival. Furthermore, assessments of numerous interventions enhancing cell survival can be done in a quantitative, serial manner in humans using cost-effective clinical imaging equipment. With medical imaging poised to play a significant role in the clinical evaluation of myocardial stem cell therapies, this SPECT imaging method could provide insightful perspectives on stem cell treatment efficacy. |
