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@ARTICLE{Krutzek:276071,
author = {F. Krutzek and C. K. Donat and M. Ullrich and K. Zarschler
and M.-C. Ludik and A. Feldmann and L. R. Loureiro and K.
Kopka$^*$ and S. Stadlbauer},
title = {{D}esign and {B}iological {E}valuation of
{S}mall-{M}olecule {PET}-{T}racers for {I}maging of
{P}rogrammed {D}eath {L}igand 1.},
journal = {Cancers},
volume = {15},
number = {9},
issn = {2072-6694},
address = {Basel},
publisher = {MDPI},
reportid = {DKFZ-2023-00977},
pages = {2638},
year = {2023},
abstract = {Noninvasive molecular imaging of the PD-1/PD-L1 immune
checkpoint is of high clinical relevance for patient
stratification and therapy monitoring in cancer patients.
Here we report nine small-molecule PD-L1 radiotracers with
solubilizing sulfonic acids and a linker-chelator system,
designed by molecular docking experiments and synthesized
according to a new, convergent synthetic strategy. Binding
affinities were determined both in cellular saturation and
real-time binding assay (LigandTracer), revealing
dissociation constants in the single digit nanomolar range.
Incubation in human serum and liver microsomes proved in
vitro stability of these compounds. Small animal PET/CT
imaging, in mice bearing PD-L1 overexpressing and PD-L1
negative tumors, showed moderate to low uptake. All
compounds were cleared primarily through the hepatobiliary
excretion route and showed a long circulation time. The
latter was attributed to strong blood albumin binding
effects, discovered during our binding experiments. Taken
together, these compounds are a promising starting point for
further development of a new class of PD-L1 targeting
radiotracers.},
keywords = {PD-L1 (Other) / PET imaging (Other) / immune checkpoint
inhibitors (Other) / organic synthesis (Other) / radiotracer
(Other) / small molecules (Other)},
cin = {DD01},
ddc = {610},
cid = {I:(DE-He78)DD01-20160331},
pnm = {899 - ohne Topic (POF4-899)},
pid = {G:(DE-HGF)POF4-899},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:37174103},
pmc = {pmc:PMC10177516},
doi = {10.3390/cancers15092638},
url = {https://inrepo02.dkfz.de/record/276071},
}