Final Report Summary - STEM CELL IMAGING (Molecular imaging of the myocardium to facilitate cardiac stem cell therapy) The goal of this grant was to develop a molecular imaging platform for noninvasive monitoring of the mechanisms involved in myocardial repair, including cell trafficking and microenvironmental conditions. In a 4-year project, researchers at Hannover Medical School (MHH) tested the central hypothesis that molecular-targeted nuclear imaging of the myocardium permits characterization of an optimal biologic environment that supports tissue recovery. The project completed 3 specific aims in a translational layout:Aim 1 was to determine the role of tissue perfusion and metabolism in the area of myocardial damage for successful subsequent regeneration. Aim 2 was to study the role of neurohumoral activation after ischemic damage for regeneration. And Aim 3 was to translate the knowledge to the clinical setting.For completion of Aim 1, extensive preparation and construction of a new preclinical molecular imaging lab was performed at MHH. Dedicated small animal PET-CT and SPECT-CT scanners were installed to provide optimal conditions for subsequent in vivo imaging work within the project.Next, dedicated imaging protocols for molecular imaging in rodents were established using the new equipment. Initial molecular targets included glucose metabolism, inflammation, perfusion. Specific anesthesia protocols for suppressing physiologic myocardial glucose utilisation in order to targetglucose uptake in inflammatory cells without interference from background signal were established. Research collaborations were established for subsequent projects targeting myocardial tissue regeneration.In parallel, clinical radionuclide imaging facilities were set up with high-end imaging technology in order to match the technology used in the preclinical lab and to thereby facilitate translation. Locoregional, national and international collaborations were strengthened in order to enable expanded preclinical work on the topic of inflammation and regeneration, and in order to achieve the goal of translation to the clinical setting. Preclinical work for Aim 2 focused on the myocardial microenvironment and its interaction with stem cell recruitment to the myocardium. Further biologic insights into the inflammatory state of the acutely infarcted myocardium were obtained in a mouse model using radiolabelled amino acid, novel radiotracer targeting the chemokine receptor CXCR4 and a complex imaging assay to specifically track endogenous bone marrow cell trafficking. This work clearly showed that cells from bone marrow contribute to myocardial inflammation andsubsequent regeneration and it provided insights into the interaction between host myocardium and systemic hematopoetic organs.Aim 3 finally focused on translating the preclinical knowledge into the clinical setting. The initial focus was on the use of the glucose analogue F-18 deoxyglucose (FDG) for imaging of myocardialinflammation, which had been established in Aim 1 in mice already. Translation was subsequently expanded toward the novel CXCR4-targeted agent, which was also successfully employed in humans after acutemyocardial infarction, in order to show activation of cytokine signalling.The entirety of this work provided unique new insights into myocardial regeneration and laid a foundation for implementation in subsequent clinical trials where the delivered imaging techniques may be used for assistance in therapeutic decision making. The ultimate goal of subsequent efforts will be to optimize regenerative therapeutic benefit based on imaging of individual myocardial biology.Contact details of the primary investigator are:Frank M. Bengel, MD, Department of Nuclear Medicine, Hannover Medical School,Carl-Neuberg-Str. 1, D-30625 Hannover, Germany; E-Mail: bengel.frank@mh-hannover.de.The project website is: http://www.mh-hannover.de/27397.html.
