Tech Briefs Magazine - December 2023 - 30

Imaging
PET imaging of tumors (dashed circles) in the body of a mouse (right in cross-section). Researchers
used a newly developed radioactive substrate to label tumor cells in a living organism. Cells genetically
modified to produce a so-called SNAP-tag enzyme took up the radioactive marker (orange),
while cells without this enzyme did not. (Image: Depke et al.)
diseases, so the research complements
each other very well.
Like all SNAP-tag substrates, the
newly developed molecule is based on
benzylguanine, to which the scientists
attached the radioactive isotope fluorine-18,
which is in turn, ideally suited
for PET imaging. The goal was to design
the synthesis in a few quick steps in order
to get as strong a signal as possible.
Because fluorine-18 has a short half-life,
its radioactivity is reduced by half after
every 110 minutes.
Initially, the scientists found that the
fluorine-18 did not attach to the desired
position on the molecule. The benzylguanine
was apparently too sensitive
to be labelled directly with fluorine-18.
So, the researchers first labelled a small
molecule that is insensitive to the necessary
chemical reactions - fluoroethylazide
- and then attached it to the
benzylguanine using a click reaction,
which is very fast and selective.
The scientists first checked whether
the synthesized substrate remained stable
when in contact with blood in the
test tube and then examined how the
cells interacted with the substrate in
the first practical tests in cell cultures.
In doing so, they compared human
tumor cells into which they had genetAvailable
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ically incorporated the SNAP-tag enzyme
with those that did not produce
the enzyme. They could see very clearly
that the radioactivity was only taken up
by the cells that produced the SNAPtag
enzyme.
Finally, the team conducted targeted
studies on individual mice because
how a molecule behaves in the complex
biological environment in a living
organism cannot be fully simulated in
cell culture or with artificially produced
organs. The scientists were able to
show that once the substrate is injected
into the bloodstream it is distributed
through the body very quickly.
Additionally, they identified the pathways
through which it is excreted. They
then compared how tumor cells with
and without the SNAP-tag enzyme reacted
to the substrate in living organisms.
For this purpose, the tumor cells were
injected under the skin of mice and removed
again after the examination in
order to confirm the results with autoradiography.
For
more information, contact
Doris Niederhoff at doris.niederhoff@
uni-munster.de.
Please visit www.techbriefs.com/webinar376
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Tech Briefs, December 2023
11/16/23 10:56 AM

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Tech Briefs Magazine - December 2023

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