10.1002/cmdc.202000820
ChemMedChem
FULL PAPER
intercalation into the lipid bilayer of the endothelial cells. On the
other hand, the achieved IC50 value of 66 nM might not be high
enough, because for a highly perfused organ with strong
metabolism rates such as the brain, even lower values are
typically beneficial to prevent a rapid wash-out. In general, the
required tracer affinity is modulated by a number of factors, such
as receptor/transporter density, the concentration and number of
endogenous ligand, which makes it difficult to predict the optimal
affinity.[2] In addition, neither too low affinities (insufficient
enrichment, fast kinetics) nor too high affinities (low kinetics) are
desirable. However, considering that cocaine was successfully
used as a PET tracer despite its IC50 of about 200 nM, an IC50 of
66 nM should be enough to achieve at least some accumulation
in the striatum, which could not be observed.[34] Therefore, the
affinity of compound 13 should not be the primary problem for
the insufficient accumulation in the brain.
Acknowledgements
This work was supported by grand CS15-033 from the Viennese
Fund for Science and Technology / WWTF (to HHS).
Conflict of Interest
The authors declare no conflict of interest.
Keywords: affinity, dopamine transporter, gallium-68, imaging
agents,
lipophilicity,
positron
emission
tomography,
radiopharmaceuticals, transporter, tropane
Conclusion
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5
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