A.5: Surface-Targeted Tracking of Individual Cells In Vivo
Participants: Günter Haufe, Johannes Eble, Ryan Gilmour, Rupert Hallmann, Uwe Karst, Friedemann Kiefer, Klaus Langer, Henning Mootz, Andrea Rentmeister, Cristian A. Strassert, Mark Waller, Bernhard Wünsch
Most currently used approaches to monitor the mobility of live cells rely on genetics for the introduction of a fluorescent tag or marker molecule into defined proteins or cell populations and subsequent imaging. Alternative strategies utilize the non-invasive introduction of reporter molecules but require the development of probes that are highly specific for a particular cell population or cellular state. CiM researchers have succeeded in generating several of such reporters, for example low molecular weight non-peptide MMP probes, RGD-based integrin specific probes, isatin-based caspase ligands and chemokine receptor ligands that have been successfully employed for FRI and PET imaging in vivo. In A.5 this probe development will be extended to new molecular targets identified in other research projects as being specific for a population of cells or a cellular process (e.g. stem and germ cell migration/differentiation, leukocyte extravasation). The novel ligands will be chemically engineered and labelled with fluorescent or radioactive moieties, and their biological, pharmacokinetic and metabolic properties will be determined. As a primary example for the development of necessary core technologies and future targeting strategies we will develop tracers for the specific in vivo labelling of highly motile macrophages that are the focus of many other research projects. Central to A.5 is the development of selective and reliable techniques for the chemical synthesis of biologically active tracers and the efficient and specific labelling of cellular processes and cells in vivo. This will contribute to the in vivo analysis of pathological and regenerative processes and will be essential for the establishment of novel imaging-based regimes for diagnosis and treatment in patients.