Method from Microscopy Used in Whole-Body Imaging

Processes and structures within the body that are normally hidden from the eye can be made visible through medical imaging. Scientists use imaging to investigate the complex functions of cells and organs and search for ways to better detect and treat diseases. In everyday medical practice, images from the body help physicians diagnose diseases and monitor whether therapies are working. To be able to depict specific processes in the body, researchers are developing new techniques for labelling cells or molecules so that they emit signals that can be detected outside the body and converted into meaningful images. A research team at the University of Münster has now adapted a cell labeling strategy currently used in microscopy – the so-called SNAP-tag technology – for use in whole-body imaging with positron emission tomography (PET) for the first time.

This method labels cells in two steps that work for completely different cell types such as tumor and inflammatory cells. First, the cells are genetically modified to produce a so-called SNAP-tag enzyme on their surface that is unique to the targeted cells. The enzyme is then brought into contact with a suitable SNAP-tag substrate. The substrate is labeled with a signal emitter and chemically structured so that it is recognized and split by the enzyme, allowing the signal emitter to be transferred to the enzyme. In the process, the enzyme is modified so that it is no longer active, and as a result, the signal emitter remains tightly coupled to it.

“Through its biological activity, the SNAP-tag enzyme labels itself, so to speak – this happens very quickly and without disturbing the natural processes in the organism,” explains Dominic Depke, a biology doctoral student and one of the lead authors of the new study.

In microscopy, fluorescent dyes are used to label cells, but they are mostly not suitable for whole-body imaging because their signals are scattered by thicker tissue layers with the result that they can no longer be measured. To solve this problem, the scientists synthesized a new SNAP-tag substrate using the radioactive signal emitter fluorine-18. The team have successfully labeled tumor cells in mice by injecting this substrate into the organism via the bloodstream and were then able to visualize the tumors using PET imaging.

“The exciting thing for us about SNAP-tag technology is that it opens up the prospect of visualizing genetically encoded cells in the body with different imaging modalities and at different temporal stages – we call it multiscale imaging,” explains nuclear medicine specialist Professor Michael Schäfers.

“Radioactive signals from fluorine-18 remain stable for only a short time,” adds radiochemist Dr. Christian Paul Konken, “but as we can repeat the second labeling step, we can potentially visualize the same cells again and again over days and weeks.”

The high level of detail provided by microscopy makes it possible to study how individual cells communicate with each other. The big picture view provided by whole-body imaging enables scientists to assess how these cells function as part of whole organ systems. Time may reveal what role individual cell types play in inflammation, for example, as it begins, continues, and resolves. “Only by combining all this information can we understand how everything is connected in the body,” says Schäfers.

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