FIGURE 3.

Cell labeling approaches and their consequences for in vivo detectability of cells. (A) Cells are directly labeled by incorporation of a contrast agent (blue) matching the desired imaging technology. Cells can either take up the contrast agent on their own (e.g. through phagocytosis, via internalizing receptors etc.) or are labeled through assisted contrast agent uptake (e.g. cell permeant contrast agents, transfection etc.). The labeled cells (blue) are administered to animals and remain traceable until the contrast agent concentration per cell becomes too dilute to be detectable. Several processes including label efflux, label dilution through cell division, and in the case of radioisotopes also radioactive decay contribute and limit the maximum observation time in vivo. (B) Scheme depicting the effects of label dilution on cell detectability. (C) Indirect cell labeling requires the incorporation of a reporter gene (green) under the control of a suitable promoter (dark green). Reporter genes are frequently introduced using viruses but can also be incorporated via episomal plasmids or gene editing. Engineered cells (green) are administered to animals and can be visualized in vivo via administration of corresponding contrast agents (purple) followed by imaging, which can be repeated to enable long-term tracking. (D) Filial generations of reporter gene expressing cells remain traceable, hence indirectly labeled cells are in vivo traceable indefinitely.